serine proteinase inhibitors


Summary: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.

Top Publications

  1. ncbi Serpin structure, mechanism, and function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, M C 536, 1819 53 West Polk Street, Chicago, Illinois 60612, USA
    Chem Rev 102:4751-804. 2002
  2. pmc SdPI, the first functionally characterized Kunitz-type trypsin inhibitor from scorpion venom
    Ruiming Zhao
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People s Republic of China
    PLoS ONE 6:e27548. 2011
  3. ncbi Serine proteinase inhibitors in arthropod immunity
    M R Kanost
    Department of Biochemistry, Kansas State University, Manhattan 66506, USA
    Dev Comp Immunol 23:291-301. 1999
  4. ncbi Isolation, expression and characterization of a novel dual serine protease inhibitor, OH-TCI, from king cobra venom
    Ying Ying He
    Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
    Peptides 29:1692-9. 2008
  5. pmc An overview of the serpin superfamily
    Ruby H P Law
    Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne VIC 3800, Australia
    Genome Biol 7:216. 2006
  6. ncbi Naturally occurring NS3-protease-inhibitor resistant mutant A156T in the liver of an untreated chronic hepatitis C patient
    Maria Cubero
    Liver Unit, Department of Medicine, Hospital Universitari Vall d Hebron, Barcelona, Spain
    Virology 370:237-45. 2008
  7. pmc Biosynthesis and structure of aeruginoside 126A and 126B, cyanobacterial peptide glycosides bearing a 2-carboxy-6-hydroxyoctahydroindole moiety
    Keishi Ishida
    Institute of Biology, Humboldt University Berlin, 10115 Berlin, Germany
    Chem Biol 14:565-76. 2007
  8. pmc Prolyl oligopeptidase induces angiogenesis both in vitro and in vivo in a novel regulatory manner
    T T Myöhänen
    Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, Helsinki, Finland
    Br J Pharmacol 163:1666-78. 2011
  9. pmc Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy
    David A Lomas
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    J Clin Invest 110:1585-90. 2002
  10. ncbi SERPINB12 is a novel member of the human ov-serpin family that is widely expressed and inhibits trypsin-like serine proteinases
    Y S Askew
    Department of Pediatrics, Harvard Medical School, Children s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 276:49320-30. 2001

Detail Information

Publications259 found, 100 shown here

  1. ncbi Serpin structure, mechanism, and function
    Peter G W Gettins
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, M C 536, 1819 53 West Polk Street, Chicago, Illinois 60612, USA
    Chem Rev 102:4751-804. 2002
  2. pmc SdPI, the first functionally characterized Kunitz-type trypsin inhibitor from scorpion venom
    Ruiming Zhao
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People s Republic of China
    PLoS ONE 6:e27548. 2011
    ..However, no Kunitz-type peptides from scorpion venom have been functionally characterized...
  3. ncbi Serine proteinase inhibitors in arthropod immunity
    M R Kanost
    Department of Biochemistry, Kansas State University, Manhattan 66506, USA
    Dev Comp Immunol 23:291-301. 1999
    ..These inhibitors may exist in plasma or in hemocyte granules. Serine proteinase inhibitors from the Kazal, Kunitz, alpha-macroglobulin, and serpin families have been identified in arthropod ..
  4. ncbi Isolation, expression and characterization of a novel dual serine protease inhibitor, OH-TCI, from king cobra venom
    Ying Ying He
    Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
    Peptides 29:1692-9. 2008
    ..46 x10(-8)M for trypsin and chymotrypsin, respectively. To our knowledge, it was the first report of Kunitz/BPTI serine proteinase inhibitor from snake venom that had equivalent trypsin and chymotrypsin inhibitory activities...
  5. pmc An overview of the serpin superfamily
    Ruby H P Law
    Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne VIC 3800, Australia
    Genome Biol 7:216. 2006
    ..Serpins are conformationally labile and many of the disease-linked mutations of serpins result in misfolding or in pathogenic, inactive polymers...
  6. ncbi Naturally occurring NS3-protease-inhibitor resistant mutant A156T in the liver of an untreated chronic hepatitis C patient
    Maria Cubero
    Liver Unit, Department of Medicine, Hospital Universitari Vall d Hebron, Barcelona, Spain
    Virology 370:237-45. 2008
    ..Here we report the presence of the A156T mutation in close to 1% of NS3 sequences within the liver quasispecies of a chronic hepatitis C patient never treated with anti-NS3-protease inhibitors...
  7. pmc Biosynthesis and structure of aeruginoside 126A and 126B, cyanobacterial peptide glycosides bearing a 2-carboxy-6-hydroxyoctahydroindole moiety
    Keishi Ishida
    Institute of Biology, Humboldt University Berlin, 10115 Berlin, Germany
    Chem Biol 14:565-76. 2007
    ..In silico analyses of the aeruginoside biosynthetic genes aerA-aerI as well as additional mutagenesis and feeding studies allowed the prediction of enzymatic steps leading to the formation of aeruginosides and the unusual Choi moiety...
  8. pmc Prolyl oligopeptidase induces angiogenesis both in vitro and in vivo in a novel regulatory manner
    T T Myöhänen
    Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, Helsinki, Finland
    Br J Pharmacol 163:1666-78. 2011
    ..Our results also advocate a role for Ac-SDKP in angiogenesis, and suggest that POP has a pro-angiogenic role via the release of Ac-SDKP from its precursor Tβ4 and POP inhibitors can block this action...
  9. pmc Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy
    David A Lomas
    Respiratory Medicine Unit, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom
    J Clin Invest 110:1585-90. 2002
  10. ncbi SERPINB12 is a novel member of the human ov-serpin family that is widely expressed and inhibits trypsin-like serine proteinases
    Y S Askew
    Department of Pediatrics, Harvard Medical School, Children s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 276:49320-30. 2001
    ..The second-order rate constants for the inhibitory reactions were 2.5 +/- 1.6 x 10(5) and 1.6 +/- 0.2 x 10(4) M(-1) S(-1), respectively. These data show that SERPINB12 encodes for a new functional member of the human ov-serpin family...
  11. ncbi Tick-Encoded serine proteinase inhibitors (serpins); potential target antigens for tick vaccine development
    A Muleng
    Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
    J Vet Med Sci 63:1063-9. 2001
  12. ncbi Sivelestat (selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagulation patients
    Mineji Hayakawa
    Emergency and Critical Care Center, Hokkaido University Hospital, Sapporo, Japan
    Shock 33:14-8. 2010
    ..The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. In addition, sivelestat administration was found to be an independent predictor of survival of those patients...
  13. ncbi Conformational properties of serine proteinase inhibitors (serpins) confer multiple pathophysiological roles
    S Janciauskiene
    Department of Medicine, Wallenberg Laboratory, Ing 46, Malmo University Hospital, S 20502, Malmo, Sweden
    Biochim Biophys Acta 1535:221-35. 2001
    b>Serine proteinase inhibitors (Serpins) are irreversible suicide inhibitors of proteases that regulate diverse physiological processes such as coagulation, fibrinolysis, complement activation, angiogenesis, apoptosis, inflammation, ..
  14. pmc The complement inhibitor FUT-175 suppresses T cell autoreactivity in experimental autoimmune encephalomyelitis
    Qing Li
    Assistant Professor, Institute of Pathology, Case Western Reserve University School of Medicine, 2085 Adelbert Road, Room 306, Cleveland, OH 44106, USA
    Am J Pathol 175:661-7. 2009
    ..These results argue that complement regulators, which inhibit C5a/C3a production, may have therapeutic efficacy in multiple sclerosis and in other clinical conditions in which T cells drive disease pathogenesis...
  15. pmc Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome
    Katiuchia Uzzun Sales
    National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
    Nat Genet 42:676-83. 2010
    ..These results uncover a pathogenic matriptase-pro-kallikrein pathway that could operate in several human skin and inflammatory diseases...
  16. ncbi Structure and function of invertebrate Kazal-type serine proteinase inhibitors
    Vichien Rimphanitchayakit
    Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Phyathai Road, Bangkok 10330, Thailand
    Dev Comp Immunol 34:377-86. 2010
    ..Silk moths produce KPIs to protect their cocoon from predators and microbial destruction...
  17. ncbi Nonstructural protein 3-4A: the Swiss army knife of hepatitis C virus
    K Morikawa
    Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
    J Viral Hepat 18:305-15. 2011
    ..This review provides a concise update on the biochemical and structural aspects of NS3-4A, its role in the pathogenesis of chronic hepatitis C and the clinical development of NS3-4A protease inhibitors...
  18. pmc Relative replication capacity and selective advantage profiles of protease inhibitor-resistant hepatitis C virus (HCV) NS3 protease mutants in the HCV genotype 1b replicon system
    Yupeng He
    Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6217, USA
    Antimicrob Agents Chemother 52:1101-10. 2008
  19. ncbi Crystal structure of textilinin-1, a Kunitz-type serine protease inhibitor from the venom of the Australian common brown snake (Pseudonaja textilis)
    Emma Karin I Millers
    School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, Australia
    FEBS J 276:3163-75. 2009
    ..5 nm versus 0.053 nm) and could also account for an observed narrower binding specificity...
  20. ncbi A tick protein with a modified Kunitz fold inhibits human tryptase
    Guido C Paesen
    CEH, Mansfield Road, Oxford, OX1 3SR, UK
    J Mol Biol 368:1172-86. 2007
    ..TdPI accumulates in the cytosolic granules of mast cells, presumably suppressing inflammation in the host animal's skin by tryptase inhibition...
  21. ncbi Structure and function of invertebrate Kunitz serine protease inhibitors
    Shiwanthi Ranasinghe
    Molecular Parasitology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    Dev Comp Immunol 39:219-27. 2013
    ..Most Kunitz inhibitors in blood sucking arthropods function as anti-coagulant factors and several act as a defense against microbial pathogen invaders...
  22. ncbi Pretreatment of sivelestat sodium hydrate improves the lung microcirculation and alveolar damage in lipopolysaccharide-induced acute lung inflammation in hamsters
    Toshiaki Iba
    Department of Surgery, Juntendo Urayasu Hospital, Juntendo University School of Medicine, Urayasu, Chiba, Japan
    Shock 26:95-8. 2006
    ..05). Pretreatment of sivelestat demonstrated a protective effect on both intravascular and extravascular damage in the lung, whereas posttreatment only suppressed the latter damage...
  23. ncbi Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase
    A Belaaouaj
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 289:1185-8. 2000
    ..coli. These findings define a mechanism of nonoxidative bacterial killing by NE and point to OmpA as a bacterial target in host defense...
  24. ncbi Osmolytes as modulators of conformational changes in serpins
    M K Chow
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
    Biol Chem 382:1593-9. 2001
    ..The implications of these results in the context of conformational changes and states adopted by alpha1-antitrypsin are discussed...
  25. pmc Serine proteases, serine protease inhibitors, and protease-activated receptors: roles in synaptic function and behavior
    Antoine G Almonte
    Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Brain Res 1407:107-22. 2011
    ..In this review, we discuss emerging roles for serine proteases in the regulation of mechanisms underlying synaptic plasticity and memory formation...
  26. ncbi Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study
    Bernhardt G Zeiher
    Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
    Crit Care Med 32:1695-702. 2004
  27. pmc Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease
    Robert B Perni
    Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, Massachusetts 02139, USA
    Antimicrob Agents Chemother 50:899-909. 2006
    ..Therefore, the overall preclinical profile of VX-950 supports its candidacy as a novel oral therapy against hepatitis C...
  28. ncbi Mechanisms of synthetic serine protease inhibitor (FUT-175)-mediated cell death
    Tadashi Uwagawa
    Department of Surgical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 109:2142-53. 2007
  29. ncbi Granzyme activity in the inflamed lung is not controlled by endogenous serine proteinase inhibitors
    G M Tremblay
    Centre de Recherche, Hopital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l Universite Laval, Sainte Foy, Quebec, Canada
    J Immunol 165:3966-9. 2000
    ..Hence, these data show that granzyme activity may be poorly controlled by protease inhibitors in inflamed tissues. Thus, granzymes could contribute to tissue remodeling and inflammation characterizing HP...
  30. ncbi Anti-hepatitis C virus drugs in development
    Esperance A K Schaefer
    Massachusetts General Hospital, Department of Medicine, Gastrointestinal Unit, Boston, USA
    Gastroenterology 142:1340-1350.e1. 2012
    ..These new reagents against hepatitis C virus should lead to highly effective, well-tolerated, and likely interferon-sparing therapies in the next several years...
  31. ncbi Sivelestat sodium hydrate improves septic acute lung injury by reducing alveolar dysfunction
    Shigeatsu Endo
    Department of Critical Care Medicine, Iwate Medical University, 19 1 Uchimaru, Morioka 020 8505, Japan
    Res Commun Mol Pathol Pharmacol 119:53-65. 2006
    ..Administration of sivelestat was found to reduce alveolar dysfunction and improve respiratory function, and it was suggested that early administration might be useful...
  32. ncbi Chymase inhibitor improves dermatitis in NC/Nga mice
    Naohiro Watanabe
    Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, Japan
    Int Arch Allergy Immunol 128:229-34. 2002
    ..To elucidate the possible role of chymase in AD, we examined the effect of a chymase inhibitor on skin lesions of NC/Nga mice...
  33. ncbi Relationship between neutrophil elastase and acute lung injury in humans
    Shouetsu Tamakuma
    National Defense Medical College, 3 2 Namiki, Tokorozawa, Saitama 359 0042, Japan
    Pulm Pharmacol Ther 17:271-9. 2004
    ..It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans...
  34. pmc Inhibition of lung serine proteases in mice: a potentially new approach to control influenza infection
    Mahmoud M Bahgat
    Department of Infection Genetics and University of Veterinary Medicine Hannover, Helmholtz Centre for Infection Research, Braunschweig, Germany
    Virol J 8:27. 2011
    ..Therefore, we studied the activity and expression of serine proteases in lungs from mice infected with influenza and evaluated the effect of serine protease inhibitors on virus replication both in cell culture and in infected mice...
  35. ncbi Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma
    Toshiaki Wakita
    Department of Molecular Pathobiology, Mie University School of Medicine, Tsu City, Mie, Japan
    Int J Cancer 108:516-23. 2004
    ..The results of our study suggest that PCI might be a potential therapeutic agent for inhibiting renal tumor invasion...
  36. pmc Antifibrinolytic role of a bee venom serine protease inhibitor that acts as a plasmin inhibitor
    Young Moo Choo
    College of Natural Resources and Life Science, Dong A University, Busan, Republic of Korea
    PLoS ONE 7:e32269. 2012
  37. ncbi The human mast cell tryptase tetramer: a fascinating riddle solved by structure
    C P Sommerhoff
    Abteilung für Klinische Chemie und Klinische Biochemie in der Chirurgischen Klinik Innenstadt, Klinikum der Ludwig Maximilians Universität, Nussbaumstrasse 20, D 80336, Munich, Germany
    Biochim Biophys Acta 1477:75-89. 2000
    ..This review solves this riddle with the help of the crystal structure of the human beta(2)-tryptase tetramer, but also indicates controversies between the unique quaternary architecture and some experimental data...
  38. pmc Anti-thrombosis repertoire of blood-feeding horsefly salivary glands
    Dongying Ma
    Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
    Mol Cell Proteomics 8:2071-9. 2009
    ..The extreme diversity of horsefly anti-thrombosis components also reveals the anti-thrombosis molecular mechanisms of the traditional Eastern medicine insect material...
  39. ncbi 4-(2-Aminoethyl)benzenesulfonyl fluoride attenuates tumor-necrosis-factor-alpha-induced blood-brain barrier opening
    P Megyeri
    Department of Pediatrics, Albert Szent Gyorgyi Medical University, Szeged, Hungary
    Eur J Pharmacol 374:207-11. 1999
    ..2 mg/kg AEBSF could significantly (P < 0.05) decrease the change in Evan's blue-albumin (MW = 67,000) transport in two regions. In conclusion, AEBSF attenuates vasogenic brain edema formation...
  40. ncbi Purification, characterization, and localization of a novel trypsin-like protease found in the human airway
    S Yasuoka
    The Department of Nursing, School of Medical Sciences, The University of Tokushima, Japan
    Am J Respir Cell Mol Biol 16:300-8. 1997
    ..These results suggest that the enzyme is secreted from submucosal serous glands onto the mucous membrane in patients with chronic airway diseases...
  41. pmc A clogged gutter mechanism for protease inhibitors
    Evette S Radisky
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 99:10316-21. 2002
    ..The arrest of enzymatic reaction at the intermediate stage allowed us to determine that the consensus nucleophilic attack angle is close to 90 degrees in the reactive Michaelis complexes...
  42. ncbi Telaprevir: a new hope in the treatment of chronic hepatitis C?
    Andrew J Fowell
    Southampton University Hospitals Trust, Southampton, UK
    Adv Ther 27:512-22. 2010
    ..In this review, we summarize the pharmacology, pharmacokinetics, and results of phase 1 and 2 clinical trials of telaprevir, and discuss the likely role of this agent in the future management of CHC...
  43. ncbi Synthesis and evaluation of the sunflower derived trypsin inhibitor as a potent inhibitor of the type II transmembrane serine protease, matriptase
    Y Q Long
    Laboratory of Medicinal Chemistry, National Cancer Institute, NIH, FCRDC, 376/208, PO Box B, Frederick, MD 21702, USA
    Bioorg Med Chem Lett 11:2515-9. 2001
    ..In addition to inhibiting trypsin, the synthetic SFTI-1 is also a very potent inhibitor, with a K(i) of 0.92nM, of the recently identified epithelial serine protease, termed 'matriptase'...
  44. ncbi Structure of a serpin-protease complex shows inhibition by deformation
    J A Huntington
    Department of Haematology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, UK
    Nature 407:923-6. 2000
    ..It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage...
  45. ncbi Structural and functional study of an Anemonia elastase inhibitor, a "nonclassical" Kazal-type inhibitor from Anemonia sulcata
    Hikaru Hemmi
    National Food Research Institute, 2 1 12 Kannondai, Tsukuba, Ibaraki 305 8642, Japan
    Biochemistry 44:9626-36. 2005
    ..7 A toward the central helix to form the introduced Cys(6)-Cys(31) bond. Such a conformational change in the restricted region correlates with the specificity change of the inhibitor...
  46. ncbi N-tosyl-L-phenylalanine chloromethyl ketone inhibits NF-kappaB activation by blocking specific cysteine residues of IkappaB kinase beta and p65/RelA
    Kyung Ho Ha
    Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137 701, Republic of Korea
    Biochemistry 48:7271-8. 2009
    ..These results suggest that TPCK inhibits NF-kappaB activation by directly modifying thiol groups on two different targets: Cys-179 of IKKbeta and Cys-38 of p65/RelA...
  47. ncbi Serine protease inhibitors nafamostat mesilate and gabexate mesilate attenuate allergen-induced airway inflammation and eosinophilia in a murine model of asthma
    Chih Lung Chen
    Division of Biomaterial and Tissue Engineering, Industrial Technology Research Institute, Hsing Chu, Taiwan, Republic of China
    J Allergy Clin Immunol 118:105-12. 2006
    ..Serine proteases such as mast cell tryptase and certain allergens are important in the pathogenesis of allergic inflammation of asthma...
  48. ncbi Comparison of textilinin-1 with aprotinin as serine protease inhibitors and as antifibrinolytic agents
    Simone Flight
    School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia
    Pathophysiol Haemost Thromb 34:188-93. 2005
    ..9 +/- 0.7). The same trend was found with the lysis of euglobulin fractions. From these data textilinin-1 appears to be a more specific plasmin inhibitor than aprotinin but aprotinin inhibits clot lysis to a greater extent...
  49. ncbi Largamides A-H, unusual cyclic peptides from the marine cyanobacterium Oscillatoria sp
    Alberto Plaza
    Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0820, USA
    J Org Chem 71:6898-907. 2006
    ..Largamides D-G (4-7) inhibited chymotrypsin with IC(50) values ranging between 4 and 25 microM...
  50. ncbi Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial
    Angelo Andriulli
    Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy
    Gastrointest Endosc 56:488-95. 2002
    ..A meta-analysis was conducted of all published studies on the use of somatostatin or gabexate for prevention of post-ERCP pancreatitis...
  51. pmc Manduca sexta serpin-6 regulates immune serine proteinases PAP-3 and HP8. cDNA cloning, protein expression, inhibition kinetics, and function elucidation
    Zhen Zou
    Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, Oklahoma 74078, USA
    J Biol Chem 280:14341-8. 2005
    ..These results suggest that serpin-6 plays important roles in the regulation of immune proteinases in the hemolymph...
  52. ncbi Location of the protease-inhibitory region of secretory leukocyte protease inhibitor
    S P Eisenberg
    Synergen Inc, Boulder, Colorado 80301
    J Biol Chem 265:7976-81. 1990
    ..Instead they suggest that leucine 72 is also the inhibitory site for trypsin, even though the amino acid residues at the inhibitory sites of other trypsin inhibitors are almost always either lysine or arginine...
  53. pmc Expression of the secretory leukoprotease inhibitor gene in epithelial cells
    T Abe
    Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892
    J Clin Invest 87:2207-15. 1991
    ..Overall, the SLPI gene appears to be a relatively nonpolymorphic, stable gene that is constitutively expressed at specific tissue sites, but has the potential to be modulated at both the transcriptional and posttranscriptional levels...
  54. ncbi Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity
    Pascal Descargues
    INSERM U563, Paul Sabatier University, Place du Dr Baylac, 31059 Toulouse, Cedex 3, France
    Nat Genet 37:56-65. 2005
    ..This work identifies LEKTI as a key regulator of epidermal protease activity and degradation of desmoglein 1 as the primary pathogenic event in Netherton syndrome...
  55. ncbi Heme oxygenase-1 gene activation by the NAD(P)H oxidase inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride via a protein kinase B, p38-dependent signaling pathway in monocytes
    Nastiti Wijayanti
    Institut für Klinische Immunologie und Transfusionsmedizin, Justus Liebig Universitat Giessen, Langhanstrasse 7, D 35392 Giessen, Germany
    J Biol Chem 280:21820-9. 2005
    ..The data suggest that the transcriptional induction of HO-1 gene expression by AEBSF is mediated via activation of a PKB, p38 MAPK signaling pathway...
  56. ncbi Identification of a serine protease as a major allergen (Per a 10) of Periplaneta americana
    V T Sudha
    Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi, India
    Allergy 63:768-76. 2008
    ..This study was undertaken to isolate and characterize a protease from Periplaneta americana and determine its allergenicity...
  57. ncbi Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohydrate recognition domain
    Tim O Hirche
    Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
    J Biol Chem 279:27688-98. 2004
    ..led to the generation of similar fragments, and cleavage was inhibited with synthetic and natural serine proteinase inhibitors. In addition, neutrophils genetically deficient in neutrophil elastase and/or cathepsin G were impaired ..
  58. ncbi Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1
    L Shapiro
    Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    FASEB J 15:115-122. 2001
    ..A novel host-pathogen interaction is suggested, and an alternative strategy to treat HIV-1-related disease may be possible...
  59. ncbi Decline in the expression of the serine proteinase inhibitor maspin is associated with tumour progression in ductal carcinomas of the breast
    N Maass
    Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Kiel, Germany
    J Pathol 195:321-6. 2001
    ..According to in vitro data, its tumour suppressor activity is likely to involve both the modulation of cell motility/invasiveness and the inhibition of angiogenesis...
  60. ncbi Prophenoloxidase-activating proteinase-3 (PAP-3) from Manduca sexta hemolymph: a clip-domain serine proteinase regulated by serpin-1J and serine proteinase homologs
    Haobo Jiang
    Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078, USA
    Insect Biochem Mol Biol 33:1049-60. 2003
    ..These data, along with our previous results on PAP-1 and PAP-2, indicate that proPO activation by PAPs is a tightly regulated process. Individual PAPs could play different roles during immune responses and developmental processes...
  61. ncbi Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains
    C W Marlor
    Institute of Bone and Joint Disease and Cancer, Bayer Corporation, West Haven, Connecticut 06516, USA
    J Biol Chem 272:12202-8. 1997
    ..The natural protein exhibited the same NH2 terminus as predicted from the cloned cDNA and inhibited trypsin, plasma kallikrein, and plasmin with IC50 values in the nanomolar range...
  62. ncbi Alpha-1-antitrypsin and a broad spectrum metalloprotease inhibitor, RS113456, have similar acute anti-inflammatory effects
    A Churg
    Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada
    Lab Invest 81:1119-31. 2001
    ..The antiproteolytic effects of these agents do not seem to be mediated by protection of endogenous alpha1AT...
  63. ncbi Serine protease activity in m-1 cortical collecting duct cells
    Lian Liu
    Department of Medicine and Physiology, Tulane University Health Science Center and VA Medical Center, New Orleans, LA 70112, USA
    Hypertension 39:860-4. 2002
    ..Steroids do not alter these effects in M-1 cells. Additional proteases are likely also present in mouse collecting duct cells...
  64. ncbi A novel serine protease inhibitor from the venom of Vespa bicolor Fabricius
    Xinbo Yang
    College of Life Sciences, Hebei Normal University, Shijiazhuang 050016, Hebei, China
    Comp Biochem Physiol B Biochem Mol Biol 153:116-20. 2009
    ..The peptide is homologous to serine protease inhibitors isolated from venoms of Anoplius samariensis and Pimpla hypochondriaca. Bicolin showed inhibitory ability against trypsin and thrombin...
  65. ncbi Textilinin-1, an alternative anti-bleeding agent to aprotinin: Importance of plasmin inhibition in controlling blood loss
    Simone M Flight
    School of Medicine, University of Queensland, Brisbane, Australia
    Br J Haematol 145:207-11. 2009
    ..Based on these data, textilinin-1 merits further investigation as a therapeutic alternative to aprotinin...
  66. ncbi Hepatitis C virus NS3/4A protease
    A D Kwong
    Vertex Pharmaceuticals, Inc, Cambridge, MA 02139, USA
    Antiviral Res 41:67-84. 1999
    ..This review will focus on the structure and function of the serine protease activity of NS3/4A and the development of inhibitors of this activity...
  67. ncbi MDCK cells that express proteases TMPRSS2 and HAT provide a cell system to propagate influenza viruses in the absence of trypsin and to study cleavage of HA and its inhibition
    Eva Böttcher
    Institut fur Virologie, Philipps Universitat Marburg, Hans Meerwein Strasse 2, 35043 Marburg, Germany
    Vaccine 27:6324-9. 2009
  68. ncbi Pathological roles of angiotensin II produced by mast cell chymase and the effects of chymase inhibition in animal models
    Mizuo Miyazaki
    Department of Pharmacology, Osaka Medical College, 2 7, Daigakumachi, Takatsuki City, Osaka 569 8686, Japan
    Pharmacol Ther 112:668-76. 2006
    ..We propose that chymase inhibitors are effective in the prevention of multiple cardiovascular disorders, especially at the local event level without any effect on the systemic blood pressure...
  69. ncbi Subcellular localization and post-secretory targeting of TgPI, a serine proteinase inhibitor from Toxoplasma gondii
    Viviana Pszenny
    Departamento de Parasitologia, ANLIS Dr Carlos G Malbran, Av Velez Sarsfield 563, 1281, Ciudad de Buenos Aires, Argentina
    Mol Biochem Parasitol 121:283-6. 2002
  70. pmc Ixodes scapularis tick serine proteinase inhibitor (serpin) gene family; annotation and transcriptional analysis
    Albert Mulenga
    Department of Entomology, Texas A and M University, 2475 TAMU, Minnie Belle Heep center, College Station, Texas 77843, USA
    BMC Genomics 10:217. 2009
    b>Serine proteinase inhibitors (Serpins) are a large superfamily of structurally related, but functionally diverse proteins that control essential proteolytic pathways in most branches of life...
  71. ncbi Complementation of intramolecular interactions for structural-functional stability of plant serine proteinase inhibitors
    Rakesh S Joshi
    Plant Molecular Biology Unit, Division of Biochemical Sciences, CSIR National Chemical Laboratory, Dr Homi Bhabha Road, Pune 411 008 MS, India
    Biochim Biophys Acta 1830:5087-94. 2013
    ..Among PIs, serine PIs (SPIs) display stability and conformational restrictions of the reactive site loop by virtue of their compact size, and by the presence of disulfide bonds, hydrogen bonds, and other weak interactions...
  72. pmc Secretory leukocyte protease inhibitor interferes with uptake of lipopolysaccharide by macrophages
    A Ding
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021, USA
    Infect Immun 67:4485-9. 1999
    ..These results suggest that the inhibitory effect of SLPI on macrophage responses to LPS may, in part, be due to its blockade of LPS transfer to soluble CD14 and its interference with uptake of LPS from LPS-sCD14 complexes by macrophages...
  73. ncbi Inhaled recombinant alpha 1-antitrypsin ameliorates cigarette smoke-induced emphysema in the mouse
    Philip A Pemberton
    Arriva Pharmaceuticals, Inc, Alameda, California 94501, USA
    COPD 3:101-8. 2006
  74. ncbi The effects of serine proteinase inhibitors on bone resorption in vitro
    A Tumber
    Department of Orthodontics and Paediatric Dentistry, United Medical and Dental Schools of Guy s, King s and St Thomas Hospitals, University of London, London SE1 9RT, UK
    J Endocrinol 178:437-47. 2003
    ..We propose that the regulation of these various enzyme systems within bone tIssue determines the sites where bone resorption will be initiated...
  75. ncbi The functional repertoire of prokaryote cellulosomes includes the serpin superfamily of serine proteinase inhibitors
    Seungha Kang
    The MAPLE Research Initiative, Department of Animal Sciences, The Ohio State University, Columbus, OH, USA
    Mol Microbiol 60:1344-54. 2006
    ..We show here with Clostridium thermocellum ATCC 27405 that members of the serpin superfamily of serine proteinase inhibitors, which are best recognized for their conformational flexibility and co-ordination of key regulatory ..
  76. ncbi Expression of LEKTI domains 6-9' in the baculovirus expression system: recombinant LEKTI domains 6-9' inhibit trypsin and subtilisin A
    Arumugam Jayakumar
    Department of Head and Neck Surgery, University of Texas, M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 4095, USA
    Protein Expr Purif 35:93-101. 2004
    ..Taking LEKTI6-9' as an example, the BEVS should facilitate the structure-function analysis of naturally occurring processed LEKTI forms that have physiological relevance...
  77. ncbi Profiling serine hydrolase activities in complex proteomes
    D Kidd
    The Skaggs Institute for Chemical Biology and Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    Biochemistry 40:4005-15. 2001
    ..Collectively, these studies demonstrate that chemical probes such as the biotinylated FPs can greatly accelerate both the functional characterization and molecular identification of active enzymes in complex proteomes...
  78. ncbi Three Kazal-type serine proteinase inhibitors from the red swamp crayfish Procambarus clarkii and the characterization, function analysis of hcPcSPI2
    Xin Cang Li
    School of Life Sciences, Shandong University, Jinan, Shandong 250100, China
    Fish Shellfish Immunol 28:942-51. 2010
    Three Kazal-type serine proteinase inhibitors, hcPcSPI2, hpPcSPI3, and hpPcSPI4, with complete cDNA sequences, were identified from a cDNA library of the red swamp crayfish, Procambarus clarkii...
  79. ncbi Nafamostat mesilate, a potent serine protease inhibitor, inhibits airway eosinophilic inflammation and airway epithelial remodeling in a murine model of allergic asthma
    Masayuki Ishizaki
    Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan
    J Pharmacol Sci 108:355-63. 2008
    ..These findings suggest that increased serine protease activity in the airways is involved in the development of antigen-induced allergic eosinophilic inflammation and epithelial remodeling in bronchial asthma...
  80. ncbi The structure of the pro-apoptotic protease granzyme B reveals the molecular determinants of its specificity
    S M Waugh
    The Graduate Group in Biophysics, University of California, San Francisco, California 94143 0446, USA
    Nat Struct Biol 7:762-5. 2000
    ..The substrate determinants found in this structure are shared by other members of this protein class and help to reveal the properties that define substrate specificity...
  81. ncbi The molecular structure of the complex of Ascaris chymotrypsin/elastase inhibitor with porcine elastase
    K Huang
    Department of Biochemistry, University of Alberta, Edmonton, Canada
    Structure 2:679-89. 1994
    ..These inhibitors share 30-40% sequence identity with one another, but have virtually no sequence identity with members of any of the other families of serine proteinase inhibitors.
  82. ncbi Bivalent inhibition of human beta-tryptase
    N Schaschke
    Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Chem Biol 8:313-27. 2001
    ..The spatial display of the four identical active sites represents an ideal basis for the rational design of bivalent inhibitors...
  83. ncbi Clinical trial of gabexate in the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis
    G S Xiong
    Department of Gastroenterology, Renji Hospital, Shanghai Second Medical University, Shanghai, People s Republic of China
    Braz J Med Biol Res 39:85-90. 2006
    ..3%) in the gabexate group and 28 (29.5%) in the placebo group (P = 0.018). The results suggest that a 4.5-h infusion of gabexate (for a total of 300 mg) could prevent post-ERCP pancreatitis and pancreatic pain...
  84. ncbi The 1.5 A crystal structure of a prokaryote serpin: controlling conformational change in a heated environment
    James A Irving
    The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, 3800, Clayton, Australia
    Structure 11:387-97. 2003
    ..These data provide evidence as to how this unusual serpin has adapted to fold and function in a heated environment...
  85. ncbi HCV-NS3 inhibitors: determination of their kinetic parameters and mechanism
    Maria Victoria Flores
    Discovery Biology Department, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK
    Biochim Biophys Acta 1794:1441-8. 2009
    ..In the case of BILN-2061, a better fit is obtained using a one-step model, indicating that the loss of potency is due to an increase in the off-rate of the EI complex...
  86. ncbi Inhibitory plant serpins with a sequence of three glutamine residues in the reactive center
    Jørn Hejgaard
    Biochemistry and Nutrition Group, BioCentrum, Technical University of Denmark, Bldg 224, DK 2800 Lyngby, Denmark
    Biol Chem 386:1319-23. 2005
  87. ncbi Changes in the expression of protease-activated receptor 1 and protease nexin-1 mRNA during rat nervous system development and after nerve lesion
    S P Niclou
    Friedrich Miescher Institut, Basel, Switzerland
    Eur J Neurosci 10:1590-607. 1998
    ..No PAR1 transcript was detected in reactive astrocytes. Similar to PAR1, PN-1 mRNA which was expressed in interneurons within the facial nucleus was also decreased following facial nerve transection...
  88. ncbi Pancreatic enzymes in the gut contributing to lung injury after trauma/hemorrhagic shock
    Han Ping Shi
    Department of General Surgery, Southern Hospital, First Military Medical University, Guangzhou 510515, China
    Chin J Traumatol 7:36-41. 2004
    ..To examine whether pancreatic proteolytic enzymes involve in lung injury induced by trauma/hemorrhagic shock (T/HS)...
  89. ncbi Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury
    Edwin A Deitch
    Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA
    Shock 19:452-6. 2003
  90. ncbi Canonical protein inhibitors of serine proteases
    D Krowarsch
    Institute of Biochemistry and Molecular Biology, University of Wroclaw, Tamka 2, 50 137 Wroclaw, Poland
    Cell Mol Life Sci 60:2427-44. 2003
    ..Serpins, similarly to the canonical inhibitors, interact with their target proteases in a substrate-like manner; however, cleavage of a single peptide bond in the binding loop leads to dramatic structural changes...
  91. pmc Structure-activity relationship and improved hydrolytic stability of pyrazole derivatives that are allosteric inhibitors of West Nile Virus NS2B-NS3 proteinase
    Shyama Sidique
    Conrad Prebys Center for Chemical Genomics, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 19:5773-7. 2009
    ..We now report the design, synthesis and in vitro evaluation of pyrazole derivatives that are inhibitors of WNV NS2B-NS3 proteinase with greatly improved stability in the assay medium...
  92. ncbi Nafamostat mesilate inhibits high-mobility group box 1 by lipopolysaccharide stimulation in murine macrophage RAW 264.7
    Satoshi Hagiwara
    Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, Yufu City, Oita, Japan
    Shock 27:429-35. 2007
    ..Our findings thus suggest that the administration of NM may therefore potentially improve the condition of patients who have septic shock...
  93. ncbi Purification, characterization and cloning of a chymotrypsin inhibitor (CI-9) from the hemolymph of the silkworm, Bombyx mori
    Ping Zhao
    The Key Sericultural Laboratory of Agricultural Ministry, Southwest University, Chongqing, 400716, China
    Protein J 26:349-57. 2007
    ..The difference of sequence and pI between CI-9 and other Kunitz type CIs indicated that it is a novel chymotrypsin inhibitor...
  94. ncbi Expression, purification and characterization of a three-domain Kazal-type inhibitor from silkworm pupae (Bombyx mori)
    Qing Liang Zheng
    College of Life Science, Zhejiang Sci Tech University, Hangzhou, China
    Comp Biochem Physiol B Biochem Mol Biol 146:234-40. 2007
    ..35 nM and the inhibitor seemed to form a 1:1 complex with subtilisin A. This is a first description of the structure and characterization of Kazal-type inhibitor with three domains cloned from silkworm pupae, B. mori...
  95. ncbi Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study
    Naoki Aikawa
    Department of Emergency and Critical Care Medicine, Keio University School of Medicine, 35 Shinano machi, Shinjuku ku, Tokyo, Japan
    Pulm Pharmacol Ther 24:549-54. 2011
    ..The Pharmaceuticals and Medical Devices Agency (PMDA) has ordered to conduct a postmarket clinical study in order to reevaluate the efficacy and safety of Sivelestat in actual clinical settings in Japan...
  96. ncbi Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma
    M T Krishna
    University of Southampton, Southampton General Hospital, Mail Point 810, Tremona Road, Southampton SO16 6YD, UK
    J Allergy Clin Immunol 107:1039-45. 2001
    ..CONCLUSION: Short-term repeated administration of APC 366 significantly reduced the magnitude of antigen-induced LAR in atopic asthmatics, which supports the role of mast cell tryptase in the pathophysiology of the LAR...
  97. ncbi Tryptase inhibition blocks airway inflammation in a mouse asthma model
    Se Woong Oh
    Department of Medicine, University of Washington, Seattle, WA 98195, USA
    J Immunol 168:1992-2000. 2002
    ..These results support tryptase as a therapeutic target in asthma and indicate that selective tryptase inhibitors can reduce allergic airway inflammation...
  98. ncbi Antiplasmin: the forgotten serpin?
    Paul B Coughlin
    Australian Centre for Blood Diseases, Monash University, Prahran
    FEBS J 272:4852-7. 2005
    ..Studies of mice with targeted deletion of antiplasmin have confirmed its importance as a major regulator of fibrinolysis and re-emphasized its value as a potential therapeutic target...
  99. ncbi Aprotinin and preservation of myocardial function after ischemia-reperfusion injury
    David A Bull
    Department of Surgery, Division of Cardiothoracic Surgery, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
    Ann Thorac Surg 75:S735-9. 2003
    ..In all, review of this topic indicates that aprotinin may reduce aspects of ischemia-reperfusion injury and prospective clinical studies are needed to evaluate the impact of aprotinin on associated patient outcomes...
  100. ncbi Crystal structure of thrombin-ecotin reveals conformational changes and extended interactions
    S X Wang
    Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, California 94143 0446, USA
    Biochemistry 40:10038-46. 2001
    ..The preference for a Val at P4 is clearly defined. The insertion at residue 60 may further affect substrate binding by moving its adjacent loops that are part of the substrate recognition sites...
  101. ncbi The absolute structural requirement for a proline in the P3'-position of Bowman-Birk protease inhibitors is surmounted in the minimized SFTI-1 scaffold
    Norelle L Daly
    Institute for Molecular Bioscience and Australian Research Council Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane, Queensland 4072, Australia
    J Biol Chem 281:23668-75. 2006
    ..Overall, this mutational analysis of SFTI-1 clearly defines the optimized nature of the SFTI-1 scaffold and demonstrates the importance of the secondary loop in maintaining the active conformation of the binding loop...

Research Grants62

  1. Therapeutic Potential of A Novel Angiogenic Inhibitor
    James Ryan; Fiscal Year: 2003
    ..It belongs to the family of serine proteinase inhibitors (serpin) and has significant sequence homology with the potent angiogenic inhibitor, PEDF...
  2. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2009
    Although protein serine proteinase inhibitors of the Kunitz, Kazal, and Bowman-Birk families make do with lock-and-key type interactions to inhibit target proteinases, serpins have now been shown by x-ray crystallography, NMR ..
  3. Serpin Modulation of Inflammatory Vasculitis; Potential for Immunomodulatory Ther
    ALEXANDRA ROSE LUCAS; Fiscal Year: 2010
    ..protease enzymes in the clot lysis pathway initiate collagen breakdown and aneurysm formation and serine proteinase inhibitors (serpins) protect against protease activation...
  4. Plasminogen activator inhibitor-1 in tumor progression and metastasis
    Yves A DeClerck; Fiscal Year: 2013
  5. Serine Proteinase Inhibitors (Serpins) in Tick Feeding and Physiology
    Albert Mulenga; Fiscal Year: 2009
    ..One important such class of proteins, are serine proteinase inhibitors that are commonly referred to by its acronym "serpin", which is the largest class of proteinase ..
    DWAIN LOUIS THIELE; Fiscal Year: 2010
    ..In proposed studies, we will determine the repertoire of serine proteinase inhibitors (serpins) expressed in normal and virally infected murine hepatocytes and determine the role of ..
    Michael Kanost; Fiscal Year: 1993
    Human plasma contains a superfamily of serine proteinase inhibitors, the serpins, which are glycoproteins of Mr = 40,000- 60,000...
  8. Poxvirus proteins involved in virion binding, membrane fusion, & entry into cells
    Richard Moyer; Fiscal Year: 2007
    ..We focus here on poxvirus- encoded serine proteinase inhibitors (serpins)...
  9. Anti-inflammatory Serpin(AAT and Elafin) Gene Transfers*
    Sihong Song; Fiscal Year: 2003
    ..Alpha 1 antitrypsin (AAT) and elafin are serine proteinase inhibitors (serpin), and have anti-inflammatory properties...
    SALVATORE PIZZO; Fiscal Year: 2001
    ..The scope of the proposal has been narrowed from previous years where projects focused on serine proteinase inhibitors, inter-alpha-trypsin inhibitor, chemically synthesized inhibitors of coagulation factors and alpha2M...
    BARRY COOPERMAN; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): Serine proteinase inhibitors (serpins) play a central role in a wide variety of physiologic processes involved in aging...
    Zygmunt Derewenda; Fiscal Year: 2000
    ..the typical GXSXG sequence motif that is present in serine hydrolases, and it is not susceptible to serine proteinase inhibitors. Histidine 58 has been implicated in the catalytic mechanism but no details are known...
    ROBERT LAVKER; Fiscal Year: 2003
    ..These studies will serve as a baseline for future studies on the therapeutic use of PAI-2 in ophthalmology. ..
  14. 3rd Intl Symp on Serpin Biology, Structure and Function
    PETER GETTINS; Fiscal Year: 2002
    ..v) To provide an opportunity for promising junior scientists and minorities to play a major role in the meeting. ..
  15. Signaling Pathways in Hepatic Fibrogenesis
    Bruce Bacon; Fiscal Year: 2005
    ..Since activated HSC play a key role in hepatic fibrogenesis, these experiments will contribute to an improved understanding of the basic biochemical processes underlying hepatic fibrosis. ..
    PETER GETTINS; Fiscal Year: 2001
    ..Olson, with interests in serpin inhibition mechanism, Dr. Patston, with interests in the structure of the serpin angiotensinogen, and Dr. Silver, who is characterizing a unique silver binding protein, silE. ..
    PETER GETTINS; Fiscal Year: 2007
    ..For antithrombins that have been activated by mutation,[unreadable] x-ray crystallography, through collaboration with Dr. Robin Carrell,[unreadable] will be used.[unreadable]..
    PETER GETTINS; Fiscal Year: 2001
    ..abstract_text> ..
  19. 900MHz NMR for Structural Biology in Chicago
    PETER GETTINS; Fiscal Year: 2007
    ..As part of the facility, a resource will be established for development of procedures for intein-based segmental isotopic labeling of proteins, as well as for production of segmentally labeled DNA and RNA species. ..
  20. Polymer Carrier for Ischemia-Inducible Gene Therapy
    David Bull; Fiscal Year: 2007
    ..abstract_text> ..
  21. Protein interactions by analytical ultracentrifugation
    PETER GETTINS; Fiscal Year: 2007
    ..The knowledge gained will be invaluable for design of therapeutics against such infections or in amelioration of diseases associated with aberrant functioning of processes such as blood coagulation. [unreadable] [unreadable] [unreadable]..
  22. Development of a combination therapy for the treatment of prostate cancer
    FRANCIS MARKLAND; Fiscal Year: 2007
    ..These studies will advance the clinical potential of this novel anticancer protein. [unreadable] [unreadable] [unreadable]..
  23. Chemoprevention Potential of Calpain Inhibitors
    ISAAC DONKOR; Fiscal Year: 2007
    ..The proposal is significant and innovative because it seeks to investigate calpain as a pharmacological target for the discovery of a new class of chemoprevention agents. [unreadable] [unreadable] [unreadable]..
    Julie Chao; Fiscal Year: 2008
    ..abstract_text> ..
    David Whitcomb; Fiscal Year: 2008
    ..The HP and familial pancreatitis studies are especially important because of the statistical power of family studies and the ability to detect modifier genes in a uniform background of susceptibility factors. ..
  26. Resolution of Gouty Inflammation
    STEPHEN MALAWISTA; Fiscal Year: 2008
    ..We suggest further that this reprogramming of lipid mediators may explain in part the action of therapeutic agents such as colchicine, and could lead to better treatment for this condition. [unreadable] [unreadable] [unreadable]..
  27. Reducing Risk Factors in Peripheral Arterial Disease
    Mary Mcgrae McDermott; Fiscal Year: 2010
  28. Molecular Genetics of Cadmium Toxicity
    Daniel W Nebert; Fiscal Year: 2010
  29. Magnetic Resonance in Peripheral Arterial Disease
    Mary Mcgrae McDermott; Fiscal Year: 2010
    ..This knowledge, in subsequent studies, is expected to lead to new therapies for PAD-related functional impairment and functional decline. ..
  30. Plasminogen activators and cerebral ischemic injury
    William M Armstead; Fiscal Year: 2010
  31. POMC Processing and Beta-Endorphine-Related Opioid Peptides
    Vivian Y H Hook; Fiscal Year: 2010
    ..New findings from this project will enhance our knowledge of the complexity of biosynthetic mechanisms for endogenous opioid and neuropeptide systems. ..
  32. Hepcidin and the pathogenesis of anemia in older adults.
    Richard D Semba; Fiscal Year: 2010
    ..This study should provide new insight into the epidemiology and biological mechanisms of anemia among older adults and help identify strategies aimed at the prevention and treatment of anemia. ..
    Yuping Wang; Fiscal Year: 2010
    ..The influence of CLP on placental sFlt-1 will be studied. Results obtained from the proposed work should enhance current knowledge of the role of the placenta and EC dysfunction in the pathogenesis of PE. ..
  34. Oxidative Stress and the Pathogenesis of Sarcopenia and Disability in Older Women
    Richard Semba; Fiscal Year: 2008
    ..AGEs are a potentially modifiable risk factor, as circulating AGEs can be lowered by dietary modification and by pharmacological intervention. ..
  35. Genetics of Asthma Severity and Lung Function Decline
    Nadia Hansel; Fiscal Year: 2008
    ..Hansel new knowledge, skills and collaborative relationships necessary to successfully apply for funding as an independent investigator during the fourth year of this award. ..
  36. Liposomal Disintegrin: Novel and Effective Antitumor Agent Phase I
    FRANCIS MARKLAND; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  37. Tissue Kallikrein, Oxidative Stress and Renal Fibrosis
    Julie Chao; Fiscal Year: 2007
    ..abstract_text> ..
    Gail Cornwall; Fiscal Year: 2005
    ..abstract_text> ..
    Richard Semba; Fiscal Year: 2005
  40. Computer Directed Photodynamic Therapy of Prostate Ca
    Jerzy Jankun; Fiscal Year: 2005
  41. Proteomics/Genomics of Opiate Analgesia and Addiction
    Vivian Hook; Fiscal Year: 2004
    ..Elucidation of distinct pathways will be significant, since it could allow future design of opiate drug regimens that provide effective analgesia, without the tolerance and dependence of addiction. ..
    Mary McDermott; Fiscal Year: 2004
    STEPHEN MALAWISTA; Fiscal Year: 2003
    ..These studies may provide the technical and conceptual basis for improvements in diagnostic and prognostic aspects of inflammatory diseases. ..
    Edwin Silverman; Fiscal Year: 2003
    ..abstract_text> ..
    ISAAC DONKOR; Fiscal Year: 2002
    ..Selected potent and cell permeable inhibitors will be tested in the rat isolated heart ischemia model for cardioprotective effect. ..
    Mary McDermott; Fiscal Year: 2001
    ..They further state that the results of this study will be used to develop subsequent intervention studies designed to improve quality of life and prevent functional decline among men and women with PAD. ..
    Judy Lieberman; Fiscal Year: 2005
    ..In vitro experiments will be performed to dissect the relative importance of signaling and perforin defects in impaired HIV-specific cytotoxicity and to explore what factors regulate and can reverse impaired CD8 T cell function. ..
  48. MMP-2 in Periodontal Disease and Oral Cancer
    Bjorn Steffensen; Fiscal Year: 2005
    Aihao Ding; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  50. Pathogenesis of Obesity and Metabolic Syndrome
    JAY HORTON; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  51. Anti-Inflammatory Role of Alpha-1 Antitrypsin in Lung
    Mark Brantly; Fiscal Year: 2006
    ..A K24 award would allow the investigator to integrate these research efforts into a mentoring program designed to interest and train young investigators in all aspects of patient-oriented research. ..
    JOHN CASIDA; Fiscal Year: 2006
  53. Taskforce for Obesity Research at Southwestern (RMI)
    JAY HORTON; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  54. Organophosphorus Pesticide Toxicology
    JOHN CASIDA; Fiscal Year: 2006
    ..Knowledge gained on OP pesticide toxicology is also applicable to OP nerve gases as chemical warfare and terrorism agents. ..
    Burton Sobel; Fiscal Year: 2006
    ..The investigators further expect that this collaborative effort will translate into a new practical clinical paradigm that will be used for treatment of Type II diabetic patients. ..
  56. A Beta Vaccination: Mechanisms and Therapautic Impact
    Lennart Mucke; Fiscal Year: 2005
    ..Lastly, the proposed project will shed light on the roles of microglia in the pathogenesis of AD-related neuronal deficits. These goals and perspectives are congruent with those of RFA AG-01-003. ..
  57. Symposium on Retinal/ Choroidal Angiogenesis
    John Penn; Fiscal Year: 2004
    ..J. Donald M. Gass, M.D. has agreed to write an introduction. In this application we request funds to support travel and registration costs of 20 young investigators and 2 keynote speakers. ..
    Vivian Hook; Fiscal Year: 2002
    ..abstract_text> ..
    Arun Ghosh; Fiscal Year: 2001
    ..Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory. ..