lactams

Summary

Summary: Cyclic AMIDES formed from aminocarboxylic acids by the elimination of water. Lactims are the enol forms of lactams.

Top Publications

  1. ncbi Gamma-lactams--a novel scaffold for highly potent and selective alpha 7 nicotinic acetylcholine receptor agonists
    Albert Enz
    Novartis Institutes for BioMedical Research, Neuroscience Disease Area, 4002 Basel, Switzerland
    Bioorg Med Chem Lett 19:1287-91. 2009
  2. pmc Mutants of Streptomyces clavuligerus with disruptions in different genes for clavulanic acid biosynthesis produce large amounts of holomycin: possible cross-regulation of two unrelated secondary metabolic pathways
    Alvaro de la Fuente
    Area de Microbiologia, Facultad de Ciencias Biologicas y Ambientales, Universidad de Leon, 24071 Leon, Spain
    J Bacteriol 184:6559-65. 2002
  3. pmc A rhodanese-like protein is highly overrepresented in the mutant S. clavuligerus oppA2::aph: effect on holomycin and other secondary metabolites production
    Nuria Nárdiz
    Area de Microbiologia, Facultad de Ciencias Biologicas y Ambientales, Universidad de Leon, 24071 Leon, Spain
    Microb Biotechnol 4:216-25. 2011
  4. pmc Antibacterial compounds from marine Vibrionaceae isolated on a global expedition
    Matthias Wietz
    National Food Institute, Technical University of Denmark, 2800 Kgs Lyngby, Denmark
    Mar Drugs 8:2946-60. 2010
  5. pmc Induction of holomycin production and complex metabolic changes by the argR mutation in Streptomyces clavuligerus NP1
    Hua Yin
    Address correspondence to Keqian Yang
    Appl Environ Microbiol 78:3431-41. 2012
  6. pmc Streptomyces clavuligerus HlmI is an intramolecular disulfide-forming dithiol oxidase in holomycin biosynthesis
    Bo Li
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Biochemistry 50:4615-22. 2011
  7. ncbi A small molecule that directs differentiation of human ESCs into the pancreatic lineage
    Shuibing Chen
    Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
    Nat Chem Biol 5:258-65. 2009
  8. ncbi Transcriptional analysis and proteomics of the holomycin gene cluster in overproducer mutants of Streptomyces clavuligerus
    V Robles-Reglero
    Area de Microbiologia, Facultad de Ciencias Biologicas y Ambientales, Universidad de Leon, 24071 Leon, Spain
    J Biotechnol 163:69-76. 2013
  9. pmc The fish pathogen Yersinia ruckeri produces holomycin and uses an RNA methyltransferase for self-resistance
    Zhiwei Qin
    Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, United Kingdom
    J Biol Chem 288:14688-97. 2013
  10. pmc A backup plan for self-protection: S-methylation of holomycin biosynthetic intermediates in Streptomyces clavuligerus
    Bo Li
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Chembiochem 13:2521-6. 2012

Detail Information

Publications244 found, 100 shown here

  1. ncbi Gamma-lactams--a novel scaffold for highly potent and selective alpha 7 nicotinic acetylcholine receptor agonists
    Albert Enz
    Novartis Institutes for BioMedical Research, Neuroscience Disease Area, 4002 Basel, Switzerland
    Bioorg Med Chem Lett 19:1287-91. 2009
    ..The cis gamma-lactam scaffold has been optimized to reveal highly potent and selective alpha7 nAChR agonists with in vitro activity and selectivity and with good brain penetration in mice...
  2. pmc Mutants of Streptomyces clavuligerus with disruptions in different genes for clavulanic acid biosynthesis produce large amounts of holomycin: possible cross-regulation of two unrelated secondary metabolic pathways
    Alvaro de la Fuente
    Area de Microbiologia, Facultad de Ciencias Biologicas y Ambientales, Universidad de Leon, 24071 Leon, Spain
    J Bacteriol 184:6559-65. 2002
    ..This enzyme forms holomycin from holothin by using acetyl coenzyme A as an acetyl group donor. The holomycin synthase activities in the different clavulanic acid mutants correlate well with their production of holomycin...
  3. pmc A rhodanese-like protein is highly overrepresented in the mutant S. clavuligerus oppA2::aph: effect on holomycin and other secondary metabolites production
    Nuria Nárdiz
    Area de Microbiologia, Facultad de Ciencias Biologicas y Ambientales, Universidad de Leon, 24071 Leon, Spain
    Microb Biotechnol 4:216-25. 2011
    ..clavuligerus...
  4. pmc Antibacterial compounds from marine Vibrionaceae isolated on a global expedition
    Matthias Wietz
    National Food Institute, Technical University of Denmark, 2800 Kgs Lyngby, Denmark
    Mar Drugs 8:2946-60. 2010
    ..halotolerans). Despite the isolation of already known antibiotics, our findings show that marine Vibrionaceae are a resource of antibacterial compounds and may have potential for future natural product discovery...
  5. pmc Induction of holomycin production and complex metabolic changes by the argR mutation in Streptomyces clavuligerus NP1
    Hua Yin
    Address correspondence to Keqian Yang
    Appl Environ Microbiol 78:3431-41. 2012
    ..clavuligerus...
  6. pmc Streptomyces clavuligerus HlmI is an intramolecular disulfide-forming dithiol oxidase in holomycin biosynthesis
    Bo Li
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Biochemistry 50:4615-22. 2011
    ....
  7. ncbi A small molecule that directs differentiation of human ESCs into the pancreatic lineage
    Shuibing Chen
    Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, Massachusetts, USA
    Nat Chem Biol 5:258-65. 2009
    ..This study describes a chemical screening platform to investigate human ESC differentiation and demonstrates the generation of a cell population that is a key milepost on the path to making beta cells...
  8. ncbi Transcriptional analysis and proteomics of the holomycin gene cluster in overproducer mutants of Streptomyces clavuligerus
    V Robles-Reglero
    Area de Microbiologia, Facultad de Ciencias Biologicas y Ambientales, Universidad de Leon, 24071 Leon, Spain
    J Biotechnol 163:69-76. 2013
    ..coelicolor M1154 strain, suggesting that heterologous expression in S. coelicolor might be toxic due to the lack of an holomycin resistance gene in this host strain...
  9. pmc The fish pathogen Yersinia ruckeri produces holomycin and uses an RNA methyltransferase for self-resistance
    Zhiwei Qin
    Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, United Kingdom
    J Biol Chem 288:14688-97. 2013
    ..Taken together, our results strongly suggest that this putative RNA methyltransferase Hom12 is the self-resistance protein that methylates the RNA of Y. ruckeri to reduce the cytotoxic effect of holomycin during holomycin production...
  10. pmc A backup plan for self-protection: S-methylation of holomycin biosynthetic intermediates in Streptomyces clavuligerus
    Bo Li
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Chembiochem 13:2521-6. 2012
    ..Furthermore, bioassays suggest that modification of the enethiol warhead by S-alkylation provides a host strategy for detoxification, one that is shared amongst multiple species producing such bioactive disulfide natural products...
  11. ncbi Antiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN α-2a/RBV in hepatitis C patients
    Edward J Gane
    Auckland Clinical Studies, New Zealand
    J Hepatol 55:972-9. 2011
    ....
  12. ncbi Antiproliferative lactams and spiroenone from adlay bran in human breast cancer cell lines
    Cheng Pei Chung
    Graduate Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan
    J Agric Food Chem 59:1185-94. 2011
    Two new lactams, coixspirolactam D (1) and coixspirolactam E (2), and a new spiroenone, coixspiroenone (3), together with seven known compounds, coixspirolactam A (4), coixspirolactam B (5), coixspirolactam C (6), coixlactam (7), coixol (..
  13. pmc Virologic escape during danoprevir (ITMN-191/RG7227) monotherapy is hepatitis C virus subtype dependent and associated with R155K substitution
    Sharlene R Lim
    InterMune, Inc, Brisbane, California, USA
    Antimicrob Agents Chemother 56:271-9. 2012
    ..These data indicate the ascendant importance of R155K for viral escape during danoprevir treatment and may have implications for the clinical use of this agent...
  14. ncbi Treatment of chronic hepatitis C patients with the NS3/4A protease inhibitor danoprevir (ITMN-191/RG7227) leads to robust reductions in viral RNA: a phase 1b multiple ascending dose study
    Nicole Forestier
    J W Goethe Universitat, Frankfurt, Germany
    J Hepatol 54:1130-6. 2011
    ..The present study assessed the safety, pharmacokinetics, and antiviral activity of danoprevir in a randomized, placebo-controlled, 14-day multiple ascending dose study in patients with chronic HCV genotype 1 infection...
  15. ncbi Design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as STAT3 inhibitors
    Cindy Gomez
    Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
    Bioorg Med Chem Lett 19:1733-6. 2009
    ..In this letter, we describe the design, synthesis, and evaluation of peptidomimetics containing Freidinger lactams as novel STAT3 inhibitors...
  16. ncbi Pramanicin induces apoptosis in Jurkat leukemia cells: a role for JNK, p38 and caspase activation
    O Kutuk
    Biological Sciences and Bioengineering Program, Sabanci University, 34956 Tuzla, Istanbul, Turkey
    Apoptosis 10:597-609. 2005
    ..These results suggest pramanicin as a potential apoptosis-inducing small molecule, which acts through a well-defined JNK- and p38-dependent apoptosis signalling pathway in Jurkat T leukemia cells...
  17. pmc Identification and characterization of NocR as a positive transcriptional regulator of the beta-lactam nocardicin A in Nocardia uniformis
    Jeanne M Davidsen
    Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA
    J Bacteriol 191:1066-77. 2009
    ..These experiments establish NocR as a positive transcriptional regulator of the nocardicin A biosynthetic pathway, coordinating the initial steps of nocardicin A biosynthesis to the production of its pHPG precursor...
  18. ncbi Synthesis of some steroidal oximes, lactams, thiolactams and their antitumor activities
    Natalija M Krstić
    Center for Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12 16, P O Box 473, 11001 Belgrade, Serbia
    Steroids 72:406-14. 2007
    ..The molecular mechanisms for apoptotic events in HeLa cell line are suggested. The guidelines for further research are underlined...
  19. ncbi The epoxy group of pramanicin is required for the optimal endothelium-dependent relaxation of rat aorta
    Chiu Yin Kwan
    Department of Medicine, Faculty of Health Sciences, McMaster University, Ontario, Canada
    J Pharmacol Sci 92:203-8. 2003
    ..The potent, selective, and irreversible inhibitory effect of PMC on the endothelial function points to its potential development into an anti-angiogenic drug...
  20. ncbi Preparation of beta- and gamma-lactams from carbamoyl radicals derived from oxime oxalate amides
    Eoin M Scanlan
    University of St Andrews, School of Chemistry, St Andrews, Fife, UK KY16 9ST
    Org Biomol Chem 2:716-24. 2004
    ..GC-MS evidence indicated that this radical cyclised to afford some of the corresponding penicillin derivative..
  21. ncbi Mutational analysis and characterization of nocardicin C-9' epimerase
    Wendy L Kelly
    Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Biol Chem 279:38220-7. 2004
    ....
  22. ncbi The biosynthetic gene cluster for a monocyclic beta-lactam antibiotic, nocardicin A
    Michele Gunsior
    Department of Chemistry, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA
    Chem Biol 11:927-38. 2004
    The monocyclic beta-lactam antibiotic nocardicin A is related structurally and biologically to the bicyclic beta-lactams comprised of penicillins/cephalosporins, clavams, and carbapenems...
  23. pmc Mutational analysis of nocK and nocL in the nocardicin a producer Nocardia uniformis
    Wendy L Kelly
    Department of Chemistry, The Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218, USA
    J Bacteriol 187:739-46. 2005
    ..Furthermore, the nocL mutant accumulated the biosynthetic intermediate nocardicin C, confirming its role as the sole oxime-forming enzyme required for production of nocardicin A...
  24. ncbi Discovery of further pyrrolidine trans-lactams as inhibitors of human neutrophil elastase (HNE) with potential as development candidates and the crystal structure of HNE complexed with an inhibitor (GW475151)
    Simon J F Macdonald
    Medicinal Chemistry 1, In Vitro Pharmacology, Systems Research, Respiratory Systems, Stevenage CEDD DMPK, United Kingdom
    J Med Chem 45:3878-90. 2002
    ..GW311616A, 1, a derivative of pyrrolidine trans-lactams, has previously been described as a potent, orally active inhibitor of human neutrophil elastase (HNE) for the ..
  25. ncbi Role of the cytochrome P450 NocL in nocardicin A biosynthesis
    Wendy L Kelly
    Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Am Chem Soc 124:8186-7. 2002
    ..This is the first gene from this pathway to be expressed and its function established, and it is the first example of oxime formation from a primary amine in bacteria unambiguously linked to a cytochrome P450...
  26. ncbi Expedient total synthesis of pyrrothine natural products and analogs
    Thomas Hjelmgaard
    Department of Natural Sciences, Bioorganic Chemistry Section, Royal Danish Veterinary and Agricultural University, DK 1871 Frederiksberg C, Denmark
    Org Biomol Chem 5:344-8. 2007
    ..The pathway proceeds via the pyrrothine hydrochloride intermediate (6 steps, 17% overall) which also gave access to very fast synthesis of analogs as demonstrated by the synthesis of , and (7 steps, 11-12% overall)...
  27. ncbi Synthesis, antiproliferative, acute toxicity and assessment of antiandrogenic activities of some newly synthesized steroidal lactams
    Neelima Dhingra
    University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India
    Eur J Med Chem 45:2229-36. 2010
    ..Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data and pharmacological screening for the synthesized compounds were reported...
  28. ncbi Synthesis and antiproliferative activity of some steroidal lactams
    Yanmin Huang
    Department of Chemistry, Guangxi Teachers Education University, Nanning 530001, China
    Steroids 76:1346-50. 2011
    ..and the cytotoxic activity against MGC 7901 and SMMC 7404 cells was not significantly different between 4-N-lactams and 3-N-lactams when its 6-substituted group was a carbonyl or a hydroximino, but all 3-N-lactams showed a higher ..
  29. ncbi Sesterterpene glycinyl-lactams: a new class of glycine receptor modulator from Australian marine sponges of the genus Psammocinia
    Walter Balansa
    Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
    Org Biomol Chem 11:4695-701. 2013
    ..The discovery and characterization of sesterterpenes 1-8, and in particular the glycinyl-lactams 3 and 6, provide valuable new insights into GlyR pharmacology...
  30. pmc In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A
    Jeanne M Davidsen
    Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA
    Chem Biol 19:297-306. 2012
    ..Conversely, production of nocardicin A was not affected by mutation of the NocB histidine motif or the R828G mutation in NocA...
  31. ncbi Organophosphorus reagents in organocatalysis: synthesis of optically active α-methylene-δ-lactones and δ-lactams
    Anna Albrecht
    Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark
    Chemistry 18:10348-54. 2012
    ..new asymmetric, catalytic strategies for the synthesis of biologically important α-methylene-δ-lactones and δ-lactams. The elaborated protocols utilize iminium-ion-mediated Michael addition of trimethyl phosphonoacetate to α,β-..
  32. ncbi Vasorelaxant effects of pramanicin, an anti-fungal agent: selective action on endothelial cells
    C Y Kwan
    Department of Medicine, Faculty of Health Sciences, Faculty of Science, McMaster University, Hamilton, Ontario, Canada
    Jpn J Pharmacol 85:234-40. 2001
    ..This is followed by a cytotoxic effect on vascular endothelial cells, eventually resulting in the loss of vasorelaxant function...
  33. pmc Non-ribosomal propeptide precursor in nocardicin A biosynthesis predicted from adenylation domain specificity dependent on the MbtH family protein NocI
    Jeanne M Davidsen
    Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States
    J Am Chem Soc 135:1749-59. 2013
    ..uniformis...
  34. pmc Stereocontrolled syntheses of peptide thioesters containing modified seryl residues as probes of antibiotic biosynthesis
    Nicole M Gaudelli
    Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA
    J Org Chem 78:6412-26. 2013
    ....
  35. ncbi Chemical and microbiologic aspects of penems, a distinct class of beta-lactams: focus on faropenem
    Jeremy M T Hamilton-Miller
    Department of Medical Microbiology, Royal Free and University College London Medical School, London, England
    Pharmacotherapy 23:1497-507. 2003
    ..Penems form a discrete class of beta-lactams that comprises structural hybrids of penicillins (penams) and cephalosporins (cephems)...
  36. ncbi Antiviral activity of danoprevir (ITMN-191/RG7227) in combination with pegylated interferon α-2a and ribavirin in patients with hepatitis C
    Nicole Forestier
    JW Goethe University Hospital, Frankfurt, Germany
    J Infect Dis 204:601-8. 2011
    ..Current therapy options for patients with chronic hepatitis C virus (HCV) infection genotype 1 are effective in <50%. Danoprevir (ITMN-191/RG7227) is a potent, selective, and orally active inhibitor of the HCV NS3/4A serine protease...
  37. ncbi Second-wave protease inhibitors: choosing an heir
    Sandra Ciesek
    Klinik fur Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Carl Neuberg Strase 1, 30625 Hannover, Germany
    Clin Liver Dis 15:597-609. 2011
    ..This article gives an overview of the compounds that will soon be available...
  38. ncbi Catalytic enantioselective conjugate reduction of lactones and lactams
    Gregory Hughes
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Am Chem Soc 125:11253-8. 2003
    ..acceleration of the enantioselective copper-catalyzed conjugate reduction of alpha,beta-unsaturated lactones, lactams, and esters is reported upon addition of alcohol additives...
  39. ncbi Ribosomal synthesis of peptides with C-terminal lactams, thiolactones, and alkylamides
    Eiji Nakajima
    Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8656, Japan
    Chembiochem 10:1186-92. 2009
    ....
  40. ncbi Biomimetic aerobic oxidation of amino alcohols to lactams
    Beneesh P Babu
    Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 106 91, Stockholm, Sweden
    Chemistry 18:11524-7. 2012
    The right path: N-protected amino alcohols undergo aerobic and biomimetic oxidation to the corresponding lactams in the presence of a ruthenium catalyst and a combination of electron-transfer mediators under air (see scheme)...
  41. ncbi Pramanicin, an antifungal agent, raises cytosolic Ca2+ and causes cell death in vascular endothelial cells
    Chiu Yin Kwan
    Department of Medicine, HSC 4N40, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5
    Vascul Pharmacol 40:35-42. 2003
    ....
  42. pmc Demonstration of microtubule-like structures formed with (-)-rhazinilam from purified tubulin outside of cells and a simple tubulin-based assay for evaluation of analog activity
    Michael C Edler
    Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA
    Arch Biochem Biophys 487:98-104. 2009
    ..This mixed polymer slowly disassembled at 0 degrees C, but there was no apparent difference in the lability of the microtubules versus the spirals...
  43. ncbi Cyclic imine nitro-Mannich/lactamization cascades: a direct stereoselective synthesis of multicyclic piperidinone derivatives
    Pavol Jakubec
    School of Chemistry, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK
    Org Lett 10:4267-70. 2008
    ..The reaction is broad in scope and stereoselective and may be coupled to an enantioselective nitroolefin Michael addition reaction as part of a highly enantio- and diastereoselective multicomponent process...
  44. ncbi Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses
    Judith M Gottwein
    Copenhagen Hepatitis C Program CO HEP, Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre and Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Gastroenterology 141:1067-79. 2011
    ..Because there are limited or no data on efficacy against HCV genotypes 2-7, we aimed at developing recombinant infectious cell culture systems expressing genotype-specific nonstructural (NS) protein 3 protease (NS3P)...
  45. ncbi Enantioselective synthesis of 3,3-disubstituted piperidine derivatives by enolate dialkylation of phenylglycinol-derived oxazolopiperidone lactams
    Mercedes Amat
    Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
    J Org Chem 72:4431-9. 2007
    The stereochemical outcome of the enolate dialkylation of simple phenylglycinol-derived oxazolopiperidone lactams is studied...
  46. ncbi Application of multicomponent reactions to antimalarial drug discovery. Part 2: New antiplasmodial and antitrypanosomal 4-aminoquinoline gamma- and delta-lactams via a 'catch and release' protocol
    Chitalu C Musonda
    Department of Chemistry, University of Cape Town, Rondebosch, South Africa
    Bioorg Med Chem 14:5605-15. 2006
    A parallel synthesis of a new series of 4-aminoquinoline gamma- and delta-lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described...
  47. ncbi Distinct endocytic pathways identified in tobacco pollen tubes using charged nanogold
    Alessandra Moscatelli
    Dipartimento di Biologia L Gorini, Universita degli Studi di Milano, Via Celoria 26, 20133 Milan, Italy
    J Cell Sci 120:3804-19. 2007
    ..However, intact positively charged-nanogold transport to vacuoles supports the idea that an endocytic pathway that does not require clathrin is also present in pollen tubes...
  48. pmc Susceptibility of treatment-naive hepatitis C virus (HCV) clinical isolates to HCV protease inhibitors
    Andrew Bae
    Department of Clinical Virology, Gilead Sciences, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 54:5288-97. 2010
    ..Our results suggest that the natural variation in baseline susceptibility may contribute to different degrees of antiviral response among patients in vivo, particularly at lower doses...
  49. ncbi Synthesis and biological evaluation of aristolactams
    Axel Couture
    Laboratoire de Chimie Organique Physique, ESA CNRS 8009, Batiment C3 2, UST Lille, F 59655 Villeneuve d Ascq Cedex, France
    Bioorg Med Chem Lett 12:3557-9. 2002
    ..Modulations were carried out on the phenanthrene nucleus and the lactam moiety as well. N-(N-dialkylaminoalkyl) derivatives exhibited interesting cytotoxic activity against the L1210 leukemia cell line...
  50. pmc Reaction discovery employing macrocycles: transannular cyclizations of macrocyclic bis-lactams
    Chong Han
    Department of Chemistry and Center for Chemical Methodology and Library Development, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA
    Org Lett 11:413-6. 2009
    Macrocyclic bis-lactams have been synthesized by cyclodimerization of homoallylic amino esters employing a Zr(IV)-catalyzed ester-amide exchange protocol...
  51. ncbi Electrophilic activation of lactams with Tf2O and pyridine: expedient synthesis of (+/-)-tetraponerine T4
    André B Charette
    Departement de Chimie, Universite de Montreal, P O Box 6128, Station Downtown, Montreal, Quebec, Canada, H3C 3J7
    Org Lett 7:5401-4. 2005
    reaction: see text] The electrophilic activation of lactams with triflic anhydride in the presence of pyridine was investigated by NMR...
  52. ncbi Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial
    Edward J Gane
    Auckland Clinical Studies, Auckland, New Zealand
    Lancet 376:1467-75. 2010
    ....
  53. ncbi Design and synthesis of pyrrolidine-5,5-trans-lactams (5-oxohexahydropyrrolo[3,2-b]pyrroles) as novel mechanism-based inhibitors of human cytomegalovirus protease. 2. Potency and chirality
    Alan D Borthwick
    Department of Medicinal Chemistry CVU UK, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK
    J Med Chem 45:1-18. 2002
    ..was obtained and used to model the conformationally restricted, chiral (S)-proline-alpha-methyl-5,5-trans-lactams into the active site groove of the enzyme, enabling us to direct and rationalize the SAR in this series...
  54. ncbi Pyrrolidine-5,5-trans-lactams as novel mechanism-based inhibitors of human cytomegalovirus protease. Part 3: potency and plasma stability
    Alan D Borthwick
    Department of Medicinal Chemistry CVU UK, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK
    Bioorg Med Chem Lett 12:1719-22. 2002
    ....
  55. ncbi Pyrrolidine-5,5-trans-lactams. 4. Incorporation of a P3/P4 urea leads to potent intracellular inhibitors of hepatitis C virus NS3/4A protease
    Martin J Slater
    GlaxoSmithKline Medicines Research Center, Gunnels Wood Road, Stevenage, SG1 2NY, UK
    Org Lett 5:4627-30. 2003
    ..Compound 7b demonstrated a 100 nM IC(50) in the replicon cell-based surrogate HCV assay...
  56. ncbi Synthesis of beta-, gamma-, and delta-lactams via Pd(II)-catalyzed C-H activation reactions
    Masayuki Wasa
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 130:14058-9. 2008
    ..The reaction protocol tolerates the presence of a double bond in the substrates. This catalytic reaction provides practical access to a wide range of beta-, gamma-, and delta-lactams.
  57. ncbi Racemic and chiral lactams as potent, selective and functionally active CCR4 antagonists
    Bradley Newhouse
    Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA
    Bioorg Med Chem Lett 14:5537-42. 2004
    A series of racemic and chiral, nonracemic lactams that display high binding affinities, functional chemotaxis antagonism, and selectivity toward CCR4 are described...
  58. ncbi Isofagomine lactams, synthesis and enzyme inhibition
    Vinni H Lillelund
    Department of Chemistry, University of Aarhus, Langelandsgade 140, DK 8000 Aarhus, Denmark
    Org Biomol Chem 1:282-7. 2003
    The synthesis of isofagomine lactams (2-oxoisofagomines) corresponding to the biologically important hexoses is presented...
  59. ncbi Intergeneric conjugation in holomycin-producing marine Streptomyces sp. strain M095
    Yan Hua Hou
    Institute of Oceanology, Chinese Academy of Sciences, Qingdao, PR China
    Microbiol Res 163:96-104. 2008
    ....
  60. pmc Role of beta-lactamases and porins in resistance to ertapenem and other beta-lactams in Klebsiella pneumoniae
    George A Jacoby
    Lahey Clinic, Burlington, Mssachusetts 01805, USA
    Antimicrob Agents Chemother 48:3203-6. 2004
    ..From a wild-type strain producing ACT-1 beta-lactamase, ertapenem-resistant mutants for which the ertapenem MICs were up to 128 microg/ml and expression of outer membrane proteins was diminished could be selected...
  61. ncbi Diastereoselective synthesis of gamma-lactams by a one-pot, four-component reaction
    Jingqiang Wei
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Org Lett 9:4077-80. 2007
    ..amines, maleic anhydrides, aldehydes, and thiols has been discovered to form tetra- and pentasubstituted gamma-lactams with high diastereoselectivity...
  62. pmc Identification of the gene cluster for the dithiolopyrrolone antibiotic holomycin in Streptomyces clavuligerus
    Bo Li
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:19731-5. 2010
    ..Purified ORF3483 shows acyltransferase activity, converting holothin to holomycin and longer acylated homologs as the last step in antibiotic assembly...
  63. ncbi Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase
    Gong Li Tang
    Division of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705, USA
    Chem Biol 11:33-45. 2004
    ..These studies unveil an unprecedented architectural complexity for the LNM hybrid NRPS-PKS megasynthetase and set the stage to investigate the molecular basis for LNM biosynthesis...
  64. ncbi Naturally occurring aristolactams, aristolochic acids and dioxoaporphines and their biological activities
    Vineet Kumar
    Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India
    Nat Prod Rep 20:565-83. 2003
    ..In this report, these three important classes of natural products are reviewed and classified on the basis of their oxygenation pattern. In addition the biological activities of these compounds and their general chemistry are discussed...
  65. ncbi P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile
    Latha G Nair
    Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 20:567-70. 2010
    SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described...
  66. ncbi Divergent structural complexity from a linear reaction sequence: synthesis of fused and spirobicyclic gamma-lactams from common synthetic precursors
    Craig E Masse
    Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    J Comb Chem 8:293-6. 2006
  67. ncbi Fast, acid-free, and selective lactamization of lactones in ionic liquids
    Kristina M Orrling
    Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Center, Uppsala University, P O Box 574, SE 751 23 Uppsala, Sweden
    J Org Chem 73:8627-30. 2008
    A fast and acid-free one-pot 0.2-30 mmol microwave methodology for direct ionic liquid-mediated preparation of lactams from lactones and primary amines has been developed...
  68. ncbi beta-lactamase as a marker for gene expression in live zebrafish embryos
    E Raz
    Institute for Biology 1, University of Freiburg, Hauptstrasse 1, Freiburg, D 79104, Germany
    Dev Biol 203:290-4. 1998
    ..We suggest that this new reporter system provides a major advancement in sensitivity over the existing methods for monitoring gene expression in vivo during early embryogenesis...
  69. pmc Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin
    T Luo
    Genetic Therapy Inc, Gaithersburg, Maryland 20879, USA
    J Virol 75:2488-92. 2001
    ..In addition, we demonstrate that IKA is also capable of efficiently blocking CD4 down-modulation in response to phorbol myristate acetate. Our data suggest that IKA may be an efficient and useful inhibitor of CCP-dependent endocytosis...
  70. ncbi Deoligomerization: a new route to lactams from unsaturated amides via radical oligomerization
    Li Liu
    Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P R China
    Org Lett 5:361-3. 2003
    ..subsequent neutralization with K(2)CO(3) led to the formation of the corresponding 5-hydroxyl-substituted delta-lactams or caprolactams, respectively...
  71. ncbi In vitro susceptibility of recent antibiotic-resistant urinary pathogens to ertapenem and 12 other antibiotics
    A Alhambra
    Department of Microbiology, Hospital de Mostoles, 28935 Móstoles, Madrid, Spain
    J Antimicrob Chemother 53:1090-4. 2004
    ..Ertapenem is a broad-spectrum 1beta-methyl carbapenem with a long plasma half-life that allows administration of a single daily dose...
  72. ncbi Exploring the effectiveness of tazobactam against ceftazidime resistant Escherichia coli: insights from the comparison between susceptibility testing and beta-lactamase inhibition
    Christopher R Bethel
    Infectious Diseases Section, Geriatrics and Extended Care, Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA
    FEMS Microbiol Lett 234:99-103. 2004
    ..The effectiveness of different formulations of piperacillin/tazobactam to other beta-lactams was compared...
  73. ncbi Synthesis and biological activity of AM-112 and related oxapenem analogues
    Iain N Simpson
    Micron Research Ltd, Ely, CB7 4JY, UK
    J Antibiot (Tokyo) 56:838-47. 2003
    ..AM-112 [(1'R,5R,6R)-2-(4-ammonio-1,1-dimethylbutyl)-6-(1'-hydroxyethyl)oxapenem-3-carboxylate] achieved the greatest protection of ceftazidime against Gram-negatives producing Class A or C beta-lactamases...
  74. ncbi New antibacterial agents derived from the DNA gyrase inhibitor cyclothialidine
    Peter Angehrn
    F Hoffmann La Roche Ltd, Pharmaceutical Division, Preclinical Research, CH 4070 Basel, Switzerland
    J Med Chem 47:1487-513. 2004
    ..By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo...
  75. ncbi Beta-lactamase stability of faropenem
    A Dalhoff
    Bayer AG Pharma Research Center, Wuppertal Germany
    Chemotherapy 49:229-36. 2003
    Faropenem (FAR) is an orally available member of the penem class unique among carbapenems and other available beta-lactams. This study compared FAR to cephalosporins and imipenem with respect to beta-lactamase (BLA) stability and ..
  76. ncbi [Comparative in vitro activity of ertapenem against aerobic and anaerobic bacteria]
    E Loza
    Servicio de Microbiologia, Hospital Universitario Ramon y Cajal, Madrid, Spain
    Rev Esp Quimioter 16:209-15. 2003
    ..5 mg/l). Both carbapenems were the most active among the tested compounds. Due to its activity against almost all pathogens studied, ertapenem appears to be an option for the treatment of mixed bacterial infections...
  77. ncbi Comparative in vitro activity of faropenem and 11 other antimicrobial agents against 250 invasive Streptococcus pneumoniae isolates from France
    J W Decousser
    Department of Hospital Health, Centre Hospitalier de Versailles, 177 rue de Versailles, 78157 Le Chesnay Cedex, France
    Eur J Clin Microbiol Infect Dis 22:561-5. 2003
    ..e., 0.25 micro g/ml for both agents). Faropenem seems to be a promising antimicrobial agent for the treatment of adult and pediatric Streptococcus pneumoniae infections...
  78. ncbi Stereoselective synthesis of the gamma-lactam hydrolysate of the thiopeptide cyclothiazomycin
    Mark C Bagley
    School of Chemistry, Cardiff University, P O Box 912, Cardiff, CF10 3TB, UK
    Org Lett 6:3401-4. 2004
    ....
  79. ncbi In vitro activity of ertapenem: review of recent studies
    Hannah M Wexler
    GLA VA Healthcare System and UCLA School of Medicine, Los Angeles, CA, USA
    J Antimicrob Chemother 53:ii11-21. 2004
    ....
  80. ncbi Intra-abdominal infections: review of the bacteriology, antimicrobial susceptibility and the role of ertapenem in their therapy
    Ellie J C Goldstein
    R M Alden Research Laboratory, Santa Monica, CA 90404, USA
    J Antimicrob Chemother 53:ii29-36. 2004
    ....
  81. ncbi Recent developments in the use of catalytic asymmetric ammonium enolates in chemical synthesis
    Matthew J Gaunt
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    Chem Rev 107:5596-605. 2007
  82. ncbi Diastereoselective cobalt-catalyzed alkylative aldol cyclizations using trialkylaluminum reagents
    Mairi E Rudkin
    School of Chemistry, University of Edinburgh, Edinburgh, UK
    Org Lett 10:2939-42. 2008
    ..These reactions provide beta-hydroxylactams containing three contiguous stereocenters with high levels of diastereoselection...
  83. ncbi Activity of three {beta}-lactams (ertapenem, meropenem and ampicillin) against intraphagocytic Listeria monocytogenes and Staphylococcus aureus
    Sandrine Lemaire
    Unité de Pharmacologie Cellulaire et Moléculaire, Universite Catholique de Louvain, Brussels, Belgium
    J Antimicrob Chemother 55:897-904. 2005
    Assessment of the activity of three beta-lactams [ertapenem (a carbapenem with a prolonged half-life), meropenem and ampicillin] against intraphagocytic Listeria monocytogenes and Staphylococcus aureus.
  84. pmc Design and synthesis of medium-ring lactam libraries inspired by octalactin a. A convergent-divergent approach
    Neil Brown
    Department of Chemistry, University of Missouri, 205 Spencer Chemical Laboratories, 5100 Rockhill Road, Kansas City, Missouri 64110, USA
    J Comb Chem 10:628-31. 2008
  85. ncbi In vitro investigation of the indirect pathogenicity of beta-lactamase-producing microorganisms in the nasopharyngeal microflora
    Satoru Kaieda
    Division of Otorhinolaryngology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852 8501, Japan
    Int J Pediatr Otorhinolaryngol 69:479-85. 2005
    ..In this study, we investigated in vitro on the indirect pathogenicities of Haemophilus parainfluenzae (H. parainfluenzae) and Moraxella catarrhalis (M. catarrhalis) against the antipneumococcul activities of some beta-lactams.
  86. ncbi [Activity of ertapenem and 19 other antimicrobial agents against beta-lactam-resistant Streptococcus pneumoniae and Haemophilus influenzae respiratory tract isolates]
    Jose Luis Gómez-Garcés
    Servicio de Microbiologia, Hospital de Mostoles, Instituto Madrileño de la Salud, Rio Jucar s n, 28935 Móstoles, Madrid, Spain
    Enferm Infecc Microbiol Clin 23:67-70. 2005
    ..Although, clinically indicated for the treatment of the polymicrobial abdominal infection, other uses are possible, due to the broad spectrum of action of this antimicrobial agent...
  87. ncbi In vitro activity of ertapenem against bacteraemic pneumococci: report of a French multicentre study including 339 strains
    Jean Winoc Decousser
    J Antimicrob Chemother 55:396-8. 2005
  88. ncbi [Investigation of the in-vitro effectiveness of ertapenem against Pseudomonas aeruginosa strains isolated from intensive care unit patients]
    Abdullah Kilic
    GATA Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dali, Ankara
    Mikrobiyol Bul 38:355-62. 2004
    ..In case of confirmation of our results by larger scale studies, the empiric treatment of ICU infections caused by P. aeruginosa with ertapenem, should be carefully evaluated...
  89. ncbi Pharmacodynamic modeling of carbapenems and fluoroquinolones against bacteria that produce extended-spectrum beta-lactamases
    Leticia R Moczygemba
    College of Pharmacy, The University of Texas at Austin, USA
    Clin Ther 26:1800-7. 2004
    ....
  90. ncbi In vitro evaluation of faropenem activity against anaerobic bacteria
    J Behra-Miellet
    Faculte de Pharmacie, 3, rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France
    J Chemother 17:36-45. 2005
    ..Only 5 strains of the Bacteroides fragilis group (1.1% of all anaerobes) were resistant to faropenem, which compared favorably with that of other reference antianaerobic drugs. The results obtained confirm those previously reported...
  91. pmc Pharmacodynamic profile of ertapenem against Klebsiella pneumoniae and Escherichia coli in a murine thigh model
    Dana Maglio
    Center for Anti Infective Research and Development, Hartford Hospital, 80 Seymour St, Hartford, CT 06102, USA
    Antimicrob Agents Chemother 49:276-80. 2005
    ..The pharmacodynamic parameter of %T>MIC(free) correlated well with bactericidal activity for all isolates, and the static and ED(80) exposures are consistent with those reported previously for carbapenems...
  92. ncbi Activity of faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains
    Ronald N Jones
    JMI Laboratories, North Liberty, IA 52317, USA
    Diagn Microbiol Infect Dis 53:311-7. 2005
    ....
  93. ncbi The glycopeptide vancomycin does not enhance toll-like receptor 2 (TLR2) activation by Streptococcus pneumoniae
    Lisa J Moore
    Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK
    J Antimicrob Chemother 54:76-8. 2004
    ..The aim of this study was to compare the activation of human TLR2 pathways after exposure of S. pneumoniae to faropenem, cefotaxime and vancomycin...
  94. ncbi Chiral dialkylaminopyridine catalysts in asymmetric synthesis
    Ryan P Wurz
    Amgen Incorporated, One Amgen Center Drive, Thousand Oaks, California 91320, USA
    Chem Rev 107:5570-95. 2007
  95. ncbi Antimicrobial susceptibility of major pathogens of orofacial odontogenic infections to 11 beta-lactam antibiotics
    T Kuriyama
    Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    Oral Microbiol Immunol 17:285-9. 2002
    ..In contrast, cefmetazole, cefoperazone/sulbactam, imipenem and faropenem were found to have greater effectiveness than penicillins...
  96. ncbi Comparative in vitro activity of faropenem against staphylococci
    Christof von Eiff
    Institute of Medical Microbiology, University of Munster, Domagkstrasse 10, 48149 Munster, Germany
    J Antimicrob Chemother 50:277-80. 2002
    ..In addition, faropenem was active against many methicillin-resistant strains of S. aureus and coagulase-negative staphylococci...
  97. ncbi In vitro activity of faropenem against 5460 clinical bacterial isolates from Europe
    Dana Milatovic
    J Antimicrob Chemother 50:293-9. 2002
  98. ncbi General microbiology and in vitro susceptibility of anaerobes isolated from complicated skin and skin-structure infections in patients enrolled in a comparative trial of ertapenem versus piperacillin-tazobactam
    Ellie J C Goldstein
    R M Alden Research Laboratory, Santa Monica, CA, 90404, USA
    Clin Infect Dis 35:S119-25. 2002
    ..9% to piperacillin-tazobactam. Ertapenem had excellent in vitro activity against the most common aerobic pathogens and almost all anaerobes recovered from patients with infections of the skin and skin structures...
  99. ncbi Comparative in vitro activity of faropenem and 11 other antimicrobial agents against 405 aerobic and anaerobic pathogens isolated from skin and soft tissue infections from animal and human bites
    Ellie J C Goldstein
    R M Alden Research Laboratory, Santa Monica UCLA Medical Center and the UCLA School of Medicine, Los Angeles, CA 90073, USA
    J Antimicrob Chemother 50:411-20. 2002
    ..three strains)...
  100. ncbi In vitro activity of ertapenem (MK-0826) against multi-drug resistant Streptococcus pneumoniae compared with 13 other antimicrobials
    Nicholaus J Hilliard
    Department of Pathology, University of Alabama at Birmingham, WP P230N, 619 19th Street South, 35249 7331, USA
    Int J Antimicrob Agents 20:136-40. 2002
    ..pneumoniae, including infections caused by organisms with reduced susceptibilities to other antimicrobial agents...
  101. ncbi Effect of protein binding on the in vitro activity and pharmacodynamics of faropenem
    F J Boswell
    Department of Microbiology, City Hospital NHS Trust, Birmingham B18 7QH, UK
    J Antimicrob Chemother 50:525-32. 2002
    ..pneumoniae strain. A significant inoculum effect was observed with all strains except S. pneumoniae. Both faropenem and amoxicillin appeared more active in 70% inactivated human serum than in Iso-Sensitest broth...

Research Grants62

  1. Defining evolutionary trajectories: Molecular adaptation to antibiotic resistance
    ADIL YOUSIF SHAMOO; Fiscal Year: 2012
    ..Bacteroides Tn4400 tetX (enzymatic inactivation of tetracyclines) and TnA TEM-1 (enzymatic inactivation of (-lactams)...
  2. CYCLE REGULATION IN THE SYMBIONT SINORHIZOBIUM MELILOTI
    KATHERINE ELISABETH GIBSON; Fiscal Year: 2011
    ..host-associated bacteria, and can thereby be applied towards development of novel targets for antimicrobial therapeutics at a time when resistance to [unreadable]-lactams and aminoglycosides is found in a variety of potent pathogens.
  3. Challenges in beta-Lactamase Mediated Resistance
    Robert A Bonomo; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Despite progress in the discovery and design of b-lactams, b-lactamases continue to pose the most significant threat to our antibiotic armamentarium...
  4. Cell wall synthesis enzymes and beta-lactam resistance in Enterococcus faecium
    Louis B Rice; Fiscal Year: 2013
    ..grown in importance as a result of its resistance to commonly used antimicrobial agents, in particular to the ?-lactams. High-level ? lactam resistance expressed by E...
  5. An Integrated Diagnostic System for Rapid Antimicrobial Susceptibility Testing
    VINCENT JEN JR GAU; Fiscal Year: 2013
    ..coli, which accounts for 85-90% of the UTIs in the community setting. Prior to the 1990s, beta-lactams such as ampicillin (AMP) were the standard antimicrobial regimen for acute uncomplicated UTIs, but was replaced ..
  6. Preserving beta-lactam utility against pathogens producing all classes of beta-la
    LUIGI XERRI; Fiscal Year: 2012
    ..inhibitors of serine-based b-lactamases (Ambler classes A, C and D), for combination with the only subclass of b-lactams (the monobactams) that are not sensitive to zinc-based enzymes (Ambler Class B)...
  7. Analysis of metallo-beta-lactamase sequence constraints at high resolution
    Timothy Palzkill; Fiscal Year: 2013
    ..to identify residue positions where the wild type amino acid is required for hydrolysis of all [unreadable]-lactams as well as positions that exhibit altered sequence requirements depending on the antibiotic used for selection, i...
  8. Novel Mechanisms of Beta-lactam Resistance in Staph Aureus
    Henry F Chambers; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): We have discovered a novel mechanism of resistance to ?-lactams that is independent of penicillinase and the low affinity penicillin bindin protein (PBP), PBP2a, the two known mechanisms of ?-lactam ..
  9. B-lactam mediated SOS response and expression of resistance in clinical MRSA
    Adriana E Rosato; Fiscal Year: 2013
    ..Diseases Control and Prevention (CDC, Atlanta, GA) as clinically relevant since exposure of such isolates to ?-lactams can result in high-level resistance (HoR)...
  10. Characterizing Beta Lactams as Neuroprotectants for Amyotrophic Lateral Sclerosis
    Jeffrey D Rothstein; Fiscal Year: 2010
    ..These sequential phases will set the stage for future practical translation towards rational clinical trial design. ..
  11. Supramolecular Complexes That Mediate Pneumococcal PG Biosynthesis and Virulence
    Malcolm E Winkler; Fiscal Year: 2012
    ..pneumoniae clinical isolates at an alarming rate. Many clinically relevant antibiotics, including [unreadable]-lactams and vancomycin, target peptidoglycan (PG) biosynthesis...
  12. Pseudomonas aeruginosa Adaptation During Early CF Airway Infection and Treatment
    Lucas R Hoffman; Fiscal Year: 2012
    ..leads to increased resistance to the three classes of antibiotic used most often in CF therapy: [unreadable]lactams, aminoglycosides, and fluoroquinolones...
  13. Developing a rapid agglutination assay for MRSA.
    NILES PATRICK DONEGAN; Fiscal Year: 2012
    ..penicillin binding proteins (PBPs) with alternative penicillin binding protein PBP2a which binds poorly to most 2-lactams. A major dilemma in the diagnosis of methicillin resistant S...
  14. Preserving beta-lactam utility vs pathogens producing any class of beta-lactamase
    LUIGI XERRI; Fiscal Year: 2013
    ..NDM-1 hydrolyzes all subclasses of [unreadable]-lactams (penicillins, cephalosporins and carbapenems) with the exception of monobactams (e.g., Aztreonam)...
  15. The Use of Polyamines in Treatment of Multidrug-Resistant Gram-Negative Pathogens
    Dong Hyeon Kwon; Fiscal Year: 2013
    ..PI discovered that exogenous polyamines (spermine, spermidine, and putrescine) in combination with 2-lactams sensitized 2- lactam resistance (become 4- to 64-fold sensitive) but in combination with polymyxin B induced ..
  16. Isolating novel fungi for antibiotic discovery
    Losee Lucy Ling; Fiscal Year: 2012
    ..Many antimicrobials, including ?-lactams and cephalosporins derive from culturable representatives of this group of microorganisms...
  17. Cranberry: Interactions with Anti-infectious Agents
    Gail Anderson; Fiscal Year: 2005
    ..bacterial pathogens in UTI are typically responsive to trimethoprim-sulfamethoxazole, quinolones, and the beta-lactams (penicillins, cephalosporins)...
  18. Novel Compounds Targeting Bacterial PBPs
    LUIGI XERRI; Fiscal Year: 2013
    ..Binding Proteins, or PBPs), but with the prospect of avoiding n important determinant of cross-resistance to ?-lactams. We have identified a novel series of highly selective, non-cytotoxic small molecule lead compounds that bind to ..
  19. Mechanism and Inhibition of Bacterial Transglycosylases and Transpeptidases.
    Suzanne Walker; Fiscal Year: 2013
    ..For example, although the TPs are the lethal targets of the beta-lactams, they remain almost completely uncharacterized...
  20. Discovery of Small Molecules that Restore Methicillin Sensitivity to MRSA
    JENNIFER CAMPBELL O apos NEILL; Fiscal Year: 2010
    ..expression of WTAs by inhibiting the first enzyme in the WTA pathway (TarO) will render MRSA susceptible to beta lactams. Consistent with this hypothesis, preliminary studies have shown that tunicamycin, a natural product that ..
  21. Molecular Archaeology: Vintage Beta Lactams for Resistant Gram Negative Infectio
    Marvin J Miller; Fiscal Year: 2013
    ..A wealth of beta-lactams were synthesized from the 1950s into the 1980s but were never developed into antimicrobial drugs...
  22. Cell-based HTS for Compounds that Block Virulence Factor Expression in MRSA
    Suzanne Walker; Fiscal Year: 2009
    ..by inhibiting one of the first two enzymes in the WTA pathway (TarO/TarA) will render MRSA susceptible to beta lactams. Consistent with this hypothesis, preliminary studies have shown that tunicamycin, a natural product that ..
  23. Epidemiology of Community-Associated, ESBL-Producing Escherichia coli
    Yohei Doi; Fiscal Year: 2010
    ..These organisms are not only resistant to most beta-lactams but also fluoroquinolones and aminoglycosides...
  24. Identifying and validating new antibiotic targets in cell wall synthesis pathways
    Suzanne Walker; Fiscal Year: 2013
    ..The proposed work grew out of recent discoveries made using [unreadable]-lactams as chemical probes of PG biosynthesis...
  25. Does ampicillin resistance or clade type determine GI colonization by E. faecium?
    KAVINDRA SINGH; Fiscal Year: 2013
    ..and perhaps entirely pbp5-R of the HA clade, has allowed this clade to replace CA strains in patients receiving ?-lactams. In Aim 1, we will investigate which colonize better: HA-clade Efm strains or CA-clade Efm strains, and then ..
  26. Novel Mechanisms of Beta-lactam Resistance in Staph Aureus
    Binh An Diep; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): We have discovered a novel mechanism (or mechanisms) of resistance to ?-lactams that is independent of the two known mechanisms of staphylococcal resistance to beta-lactams: pencillinase and PBP2a...
  27. A Mechanism-Based Approach to Metallo-beta-Lactamase Inhibition
    Alejandro J Vila; Fiscal Year: 2013
    ..Therefore, our investigations will test the following hypotheses: 1) structurally divergent MBLs hydrolyze b-lactams, especially carbapenems, by proceeding through common reaction intermediates;2) the mobile loops flanking the ..
  28. BIOSYNTHESIS OF BETA-LACTAM ANTIBIOTICS
    CRAIG ARTHUR TOWNSEND; Fiscal Year: 2013
    ..beta-lactamase enzymes and a wide-spread source of resistance, (2) the nocardicins, a family of monocyclic beta-lactams, and the metabolically related monobactams, and (3) the carbapenems, represented clinically by thienamycin and ..
  29. Novel Metallo-beta-lactamase Inhibitors
    LUIGI XERRI; Fiscal Year: 2012
    ..is an urgent need for new initiatives to address this growing issue and protect the lifespan of all [unreadable]-lactams. This Phase I SBIR Application focuses on the advancement of a novel first-in-class chemical series of potent ..
  30. Protein-protein interaction essential for bacterial growth and virulence
    Mark A Saper; Fiscal Year: 2013
    ..Moreover, the mode of ac- tion of such an inhibitor would be complementary with, but different from, ?-lactams.
  31. The Continuing Challenge of Carbapenemases in K. pneumoniae: KPC-2 &NDM-1
    Robert A Bonomo; Fiscal Year: 2013
    ..e., carbapenem-hydrolyzing [unreadable]-lactamases) that potentially inactivate all [unreadable]-lactams severely limit the antimicrobials available to treat infections with these bacteria...
  32. Harvard-wide Program on Antibiotic Resistance
    Suzanne Walker; Fiscal Year: 2013
    ..aureus could be successfully treated with b-lactams in C. elegans and murine models respectively...
  33. Regulation of P. aeruginosa PoxB Oxacillinase by AmpR and a Two-Component System
    Kalai Mathee; Fiscal Year: 2011
    ..selection of strains that overproduce AmpC [unreadable]-lactamase, an enzyme that hydrolyzes the [unreadable]-lactams, contributes to both morbidity and mortality. Previous studies investigating the regulation of the amp genes in P...
  34. Structure, Function and Inhibition of Beta-lactamases
    Brian K Shoichet; Fiscal Year: 2013
    ..In the last 25 years, hundreds of mutant ?-lactamases have appeared in the clinic in response to newer ?-lactams. These enzymes are a pressing medical problem and a fascinating example of molecular evolution...
  35. The use of mass spectrometry for rapid detection of carbapenemase-producing bacte
    DAVID RYAN PEAPER; Fiscal Year: 2013
    ..MDR GNRs expressing extended spectrum beta-lactamases (ESBLs) capable of hydrolyzing all non-carbapenem beta-lactams. However, their effectiveness has been compromised by the recent emergence of plasmid-encoded carbapenemases...
  36. Effecting C-O activation of oxazolidinones by Ni to construct small, chiral heter
    MATTHEW STEVEN WINSTON; Fiscal Year: 2012
    ..transformation of chiral oxazolidinones to small chiral heterocycles, such as aziridines and [unreadable]-lactams, will be developed...
  37. Pilot Scale Libraries Inspired by Natural Products
    JEFFREY AUBE; Fiscal Year: 2012
    ..amines, indoles, or other heterocyclic products, (2) libraries based on a recently reported class of twisted lactams, (3) libraries inspired by synthetic routes toward marine alkaloids of the cylindricine/lepadiformine class, (4) ..
  38. NUCLEIC ACID PROBES OF RIBOSOMAL STRUCTURE AND FUNCTION
    BARRY COOPERMAN; Fiscal Year: 2003
    ..Interest in these ribosomal antibiotics has been growing as bacterial resistance to beta-lactams and quinolines has become more widespread...
  39. HTS assay and configuration for inhibitors of the UDP-Mur formation pathway
    Michael McNeil; Fiscal Year: 2009
    ..synthesis is a well established mode of action of effective antibacterial and is primarily accomplished with 2-lactams and vancomycin. However, M...
  40. REACTIVITY MODELS FOR ISOPENICILLIN N SYNTHETASE
    PATRICIA SHAPLEY; Fiscal Year: 1992
    ..for beta-hydride elimination form coordinated cysteine to the metal, (3) to induce the formation of beta-lactams and beta-lactones at the metal center, and (4) to prepare oxo-iron alkyls and study chemical reactions resulting ..
  41. Enantioselective Thiourea-Catalyzed Syntheses of beta-Lactones and beta-Lactams
    PAMELA MICHELE TADROSS; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Lactones and -lactams are structural motifs critical to the treatment of disease and infection whose activity is directly related to the highly strained 4-membered ring present in each...
  42. H. INFLUENZAE: PENICILLIN BINDING PROTEINS & CELL WALL
    Paul Mendelman; Fiscal Year: 1991
    ..influenzae disease. However, the mode of action of beta-lactams on the cell wall of this pathogen is undetermined at the biochemical level...
  43. New Drug for Treatment of Chronic Bacterial Infection
    Gyanu Lamichhane; Fiscal Year: 2013
    ..One the most successful class of antibiotics in human clinical use, namely the [unreadable]-lactams and cephalosporins, targets the classical 4?3 linkages...
  44. Novel antibacterials targeting the 50S ribosomal subunit
    Joyce Sutcliffe; Fiscal Year: 2005
    ..Looking ahead, this agent would cover strains that have resistance to macrolides, quinolones, vancomycin, ¿-lactams, Synercid(r), and Linezolid...
  45. REGULATION OF BETA-LACTAMASE IN STAPHYLOCOCCUS AUREUS
    Corinne Hackbarth; Fiscal Year: 2000
    ..of beta-lactamase, which degrades penicillin, and PBP2a, a cell wall synthesis enzyme with low affinity for beta-lactams, is inducible upon exposure to beta-lactams, and regulation involves a putative repressor protein (BlaI) and a ..
  46. BIOSYNTHESIS OF BETA LACTAM ANTIBIOTICS
    Craig Townsend; Fiscal Year: 2003
    ..beta-lactamase enzymes and a wide-spread source of resistance, (2) the nocardicins, a family of monocyclic beta-lactams, and the metabolically related monobactams, and (3) the carbapenems, represented clinically by thienamycin and ..
  47. Complex Heterocycles and Hybrid Strategies for Pilot Scale Libraries
    Mark J Kurth; Fiscal Year: 2012
    ..Our aims are to synthesize (1) 440 diverse lactams that emanate from multicomponent reactions and formal cycloadditions employing anhydrides, (2) 308 ..
  48. Detection of Antibiotic Resistance Genes in Bacterial Agents of Hospital-Acquired
    Andrew Levin; Fiscal Year: 2009
    ..of microorganisms and genetic determinants of antibiotic resistance, including resistance to [unreadable]-lactams and fluoroquinolones in Gram-negative bacteria, and to methicillin and vancomycin in Gram-positive bacteria...
  49. NOVEL LINKAGES OF THE PEPTIDOGLYCAN LAYER: ADAPTATION &RESISTANCE TO B-LACTAMS
    Gyanu Lamichhane; Fiscal Year: 2011
    ..The beta-lactams, the most widely used antibacterial drugs, target the 4-->3 linkages...
  50. Antibiotic Hypersusceptibility Mutations in Bacteria
    Alexander Mankin; Fiscal Year: 2005
    ..Application of this strategy will identify multiple mutations increasing bacterial susceptibility to beta-lactams (ampicillin, ceftazidime, imipenem), translational inhibitors (erythromycin, linezolid, tetracycline, and ..
  51. MORPHOGENESIS OF THE MUREIN SACCULUS OF ESCHERICHIA COLI
    Michael Hochberg; Fiscal Year: 1990
    ..This same ability to regulate murein synthesis is reflected in the sensitivity of bacteria to B-lactams antibiotics; bacteria which are not growing are resistant to most penicillin and cephalosporins and conversely ..
  52. METALLO BETA LACTAMASE FROM X MALTOPHILIA
    Michael Crowder; Fiscal Year: 2002
    Enzymes that hydrolyze beta-lactams and cephalosporin antibiotics are called beta-lactamases, and their production by bacteria is the most common way that bacteria become antibiotic-resistant...
  53. MOLECULAR GENETICS OF PLASMID-DETERMINED BETA-LACTAMASE
    George Jacoby; Fiscal Year: 1990
    ..are related genetically, what structural features are responsible for their ability to hydrolyze particular beta-lactams, and what is their further potential for evolution in response to the changing selection pressure imposed by the ..
  54. 400 MHz NMR Spectrometer for Shared Use
    Craig Townsend; Fiscal Year: 2004
    ..3) development of catalytic, asymmetric processes to synthesize beta-lactams and beta-amino acids and the introduction of fluorine...
  55. MECHANISMS OF GLYCOPEPTIDE RESISTANCE IN STAPHYLOCOCCI
    Robert Daum; Fiscal Year: 2006
    ..aureus isolates that are resistant to methicillin, cross resistant to all beta-lactams, and often resistant to a wide spectrum of unrelated antimicrobials...
  56. Allylsilane Annulation Strategy for Diversity Synthesis
    ANNALIESE FRANZ; Fiscal Year: 2004
    ..as tetrahydrofurans, pyrrolidines, pyrrolidinones, isoxazolidines, quinone derivatives, tetrahydroquinolines, lactams, and cyclopentane rings, as well as homoallylic alcohols and peptidomimetics...
  57. STRUCTURE/FUNCTION OF ENGINEERED B LACTAMASES
    Osnat Herzberg; Fiscal Year: 2002
    ..A mutant beta-lactamase that has lost its ability to hydrolyze beta-lactams and instead is inhibited by these compounds will be further altered to introduce a new deacylation mechanism that ..
  58. ROUTES TO CHIRAL CARBOCYCLIC AND HETEROCYCLIC COMPOUNDS
    A Meyers; Fiscal Year: 2000
    The extraordinary success realized by probing the chemistry of chiral, non-racemic bicyclic lactams over the past dozen years requires us to continue the investigation for one more year...
  59. SEMISYNTHETIC TAXOL DERIVATIVES
    Gunda Georg; Fiscal Year: 1992
    ..The key reaction is an enolate imine condensation to form beta-lactams, which can then be hydrolyzed to produce the desired 3- phenylisoserine...
  60. CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES
    Michael Doyle; Fiscal Year: 2002
    ..that have been used for the construction of lignans, 2-deoxyxylolactone, and a variety of lactones and lactams in high enantiomeric excess (94 percent or more ee) with exceptional diastereo-, regio-, and chemoselectivity...
  61. SYNTHESIS OF MACROCYCLIC NATURAL PRODUCTS
    Paul Bartlett; Fiscal Year: 1980
    ..In addition, a procedure for the synthesis of large-ring lactams via the Claisen rearrangement of N-allyl amides will also be investigated.
  62. NEW ASYMMETRIC PROCESSES FOR USE IN ORGANIC SYNTHESIS
    K Sharpless; Fiscal Year: 1999
    ..g. beta-lactams, diltiazem, brassinolide, antibiotic AT-125, cianidanol, etc.)...