pterins

Summary

Summary: Compounds based on 2-amino-4-hydroxypteridine.

Top Publications

  1. ncbi Glucocorticoids inhibit tetrahydrobiopterin-dependent endothelial function
    D G Johns
    Department of Physiology, Medical College of Georgia, Augusta 30912-3000, USA
    Exp Biol Med (Maywood) 226:27-31. 2001
  2. ncbi Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function
    Mathew Eric Hyndman
    Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1
    Am J Physiol Heart Circ Physiol 282:H2167-72. 2002
  3. ncbi Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease
    Nicholas J Alp
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
    Arterioscler Thromb Vasc Biol 24:413-20. 2004
  4. ncbi Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations
    M M Verbeek
    Department of Laboratory of Pediatrics, Radboud University Nijmegen Medical Centre, Donders Centre for Neuroscience, The Netherlands
    Mol Genet Metab 95:127-32. 2008
  5. ncbi Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from D. gigas
    M J Romao
    Instituto de Tecnologia Quimica e Biologica, Oeiras, Portugal
    Science 270:1170-6. 1995
  6. pmc Decreased tetrahydrobiopterin and disrupted association of Hsp90 with eNOS by hyperglycemia impair myocardial ischemic preconditioning
    Nikolina Vladic
    Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Am J Physiol Heart Circ Physiol 301:H2130-9. 2011
  7. pmc Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms
    Julien Amour
    Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Anesthesiology 112:576-85. 2010
  8. ncbi Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase
    M K Chan
    Division of Chemistry and Chemical Engineering, Pasadena, CA 91125
    Science 267:1463-9. 1995
  9. ncbi Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: a new phenotype
    N Blau
    Division of Clinical Chemistry and Biochemistry, University Children s Hospital, Zurich, Switzerland
    Neurology 61:642-7. 2003
  10. ncbi Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies
    G Shi
    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA
    J Med Chem 44:1364-71. 2001

Research Grants

Detail Information

Publications205 found, 100 shown here

  1. ncbi Glucocorticoids inhibit tetrahydrobiopterin-dependent endothelial function
    D G Johns
    Department of Physiology, Medical College of Georgia, Augusta 30912-3000, USA
    Exp Biol Med (Maywood) 226:27-31. 2001
    ..We conclude that inhibition of BH4 synthesis by glucocorticoid regulation of GTP cyclohydrolase expression may contribute to reduced endothelium-dependent vasodilation characteristic of glucocorticoid-induced hypertension...
  2. ncbi Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function
    Mathew Eric Hyndman
    Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1
    Am J Physiol Heart Circ Physiol 282:H2167-72. 2002
    ..superoxide) production and improve endothelial function. 5-Methyltetrahydrofolate may represent an important strategy for intervention aimed at improving tetrahydrobiopterin bioavailability...
  3. ncbi Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease
    Nicholas J Alp
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
    Arterioscler Thromb Vasc Biol 24:413-20. 2004
    ..Thus, BH4 represents a potential therapeutic target in the regulation of eNOS function in vascular disease...
  4. ncbi Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations
    M M Verbeek
    Department of Laboratory of Pediatrics, Radboud University Nijmegen Medical Centre, Donders Centre for Neuroscience, The Netherlands
    Mol Genet Metab 95:127-32. 2008
    ..5-MTHF) deficiency, strongly relies on a robust analysis of neurotransmitter metabolites, pterins and 5-MTHF in the cerebrospinal fluid (CSF)...
  5. ncbi Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from D. gigas
    M J Romao
    Instituto de Tecnologia Quimica e Biologica, Oeiras, Portugal
    Science 270:1170-6. 1995
    ..The molybdopterin dinucleotide is deeply buried in the protein. The cis-dithiolene group of the pyran ring binds the molybdenum, which is coordinated by three more (oxygen) ligands...
  6. pmc Decreased tetrahydrobiopterin and disrupted association of Hsp90 with eNOS by hyperglycemia impair myocardial ischemic preconditioning
    Nikolina Vladic
    Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Am J Physiol Heart Circ Physiol 301:H2130-9. 2011
    ..The results suggest that eNOS dysregulation may be a central mechanism of impaired cardioprotection during hyperglycemia...
  7. pmc Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms
    Julien Amour
    Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Anesthesiology 112:576-85. 2010
    ..The authors tested the hypothesis that hyperglycemia abolishes anesthetic preconditioning (APC) through BH4- and heat shock protein 90-dependent pathways...
  8. ncbi Structure of a hyperthermophilic tungstopterin enzyme, aldehyde ferredoxin oxidoreductase
    M K Chan
    Division of Chemistry and Chemical Engineering, Pasadena, CA 91125
    Science 267:1463-9. 1995
    ..These properties may contribute to the extreme thermostability of this enzyme...
  9. ncbi Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: a new phenotype
    N Blau
    Division of Clinical Chemistry and Biochemistry, University Children s Hospital, Zurich, Switzerland
    Neurology 61:642-7. 2003
    ..To describe three unrelated children with a distinctive variant of Aicardi-Goutières syndrome (AGS) characterized by microcephaly, severe mental and motor retardation, dyskinesia or spasticity, and occasional seizures...
  10. ncbi Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies
    G Shi
    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA
    J Med Chem 44:1364-71. 2001
    ....
  11. ncbi HPLC with electrochemical and fluorescence detection procedures for the diagnosis of inborn errors of biogenic amines and pterins
    Aida Ormazabal
    Department of Clinical Chemistry, Hospital Sant Joan de Deu, Esplugues, Barcelona, Spain
    J Neurosci Methods 142:153-8. 2005
    The analysis of biogenic amines (BA) and pterins in cerebrospinal fluid (CSF) is essential for the early diagnosis of neurotransmission defects in the paediatric age...
  12. pmc Chronic oral supplementation with sepiapterin prevents endothelial dysfunction and oxidative stress in small mesenteric arteries from diabetic (db/db) mice
    Malarvannan Pannirselvam
    Smooth Muscle Research Group, The University of Calgary, Alberta, Canada
    Br J Pharmacol 140:701-6. 2003
    ..Furthermore, these results suggest that decreased biosynthesis of BH4 may not be the basis for endothelial dysfunction in SMA from db/db mice...
  13. ncbi Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase
    A Achari
    Glaxo Wellcome Research and Development, Beckenham, Kent, UK
    Nat Struct Biol 4:490-7. 1997
    ..The 7,8-dihydropterin pyrophosphate (DHPPP) substrate binds in a deep cleft in the barrel, whilst sulfanilamide binds closer to the surface. The DHPPP ligand site is highly conserved amongst prokaryotic and eukaryotic DHPSs...
  14. ncbi The structure and function of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Haemophilus influenzae
    M Hennig
    F Hoffmann La Roche Ltd, Pharma Preclinical Research, Basel, CH 4070, Switzerland
    J Mol Biol 287:211-9. 1999
    ..The three-dimensional structure of a binary complex has been refined at 2.1 A resolution. The location of the substrate analog and a sulfate ion gives important insight into the molecular mechanism of the enzyme...
  15. ncbi 2.0 A X-ray structure of the ternary complex of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a substrate analogue
    D K Stammers
    Glaxo Wellcome R and D, Medicines Research Centre, Stevenage, UK
    FEBS Lett 456:49-53. 1999
    ....
  16. ncbi Tetrahydrofolate-specific enzymes in Methanosarcina barkeri and growth dependence of this methanogenic archaeon on folic acid or p-aminobenzoic acid
    Bärbel Buchenau
    Max Planck Institut für Terrestrische Mikrobiologie and Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps Universitat, Karl von Frisch Strasse, Marburg, Germany
    Arch Microbiol 182:313-25. 2004
    ..The presence of both H4SPT and H4F in M. barkeri is in agreement with earlier isotope labeling studies indicating that there are two separate C1 pools in these methanogens...
  17. ncbi The role of reduced pterins in resistance to reactive oxygen and nitrogen intermediates in the protozoan parasite Leishmania
    Wilfried Moreira
    Centre de Recherche en Infectiologie du CHUL, Universite Laval, Quebec, QC G1V 4G2, Canada
    Free Radic Biol Med 46:367-75. 2009
    ..Reduced pterins are known scavengers of reactive oxygen and nitrogen intermediates...
  18. ncbi Essential roles of a dynamic loop in the catalysis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
    Jaroslaw Blaszczyk
    Macromolecular Crystallography Laboratory, National Cancer Institute, P O Box B, Frederick, Maryland 21702, USA
    Biochemistry 43:1469-77. 2004
    ..The loop plays an important role in the stabilization of the ternary complex and is critical for catalysis...
  19. ncbi Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution
    J Blaszczyk
    Program in Structural Biology National Cancer Institute Frederick Cancer Research and Development Center 21702, Frederick, MD 21702, USA
    Structure 8:1049-58. 2000
    ..Crystal structures have been reported for HPPK without bound ligand, containing an HP analog, and complexed with an HP analog, two Mg(2+) ions, and ATP...
  20. pmc Structural studies of pterin-based inhibitors of dihydropteroate synthase
    Kirk E Hevener
    Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 847 Monroe Avenue, Room 327 Johnson Building, Memphis, Tennessee 38163, USA
    J Med Chem 53:166-77. 2010
    ....
  21. ncbi Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics
    Jaroslaw Blaszczyk
    Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA
    Acta Crystallogr D Biol Crystallogr 63:1169-77. 2007
    ..Therefore, these structural and biochemical data are valuable for the design of novel medical countermeasures against plague...
  22. ncbi An Fe2+-dependent cyclic phosphodiesterase catalyzes the hydrolysis of 7,8-dihydro-D-neopterin 2',3'-cyclic phosphate in methanopterin biosynthesis
    Zahra Mashhadi
    Department of Biochemistry 0308, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA
    Biochemistry 48:9384-92. 2009
    ..0 mol of zinc and 0.8 mol of iron per protomer. MptB requires Fe(2+) for activity, the same as observed for MptA. Thus the first two enzymes involved in H(4)MPT biosynthesis in the archaea are Fe(2+) dependent...
  23. ncbi Elucidation of methanogenic coenzyme biosyntheses: from spectroscopy to genomics
    David E Graham
    Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg 24061 0308, USA
    Nat Prod Rep 19:133-47. 2002
    ..The literature from 1971 to September 2001 is reviewed, and 169 references are cited...
  24. ncbi Escherichia coli 6-pyruvoyltetrahydropterin synthase ortholog encoded by ygcM has a new catalytic activity for conversion of sepiapterin to 7,8-dihydropterin
    Hyun Joo Woo
    Department of Microbiology, Inje University, 621 749, Kimhae, South Korea
    FEBS Lett 523:234-8. 2002
    ..The same activity, however, was also detected in a PTPS ortholog of Synechocystis sp. PCC 6803 but not significant in Drosophila and human enzymes, suggesting that the activity may be prevalent in bacterial PTPS orthologs...
  25. ncbi Characterization of an Fe(2+)-dependent archaeal-specific GTP cyclohydrolase, MptA, from Methanocaldococcus jannaschii
    Laura L Grochowski
    Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA
    Biochemistry 46:6658-67. 2007
    The first step in the biosynthesis of pterins in bacteria and plants is the conversion of GTP to 7,8-dihydro-d-neopterin triphosphate catalyzed by GTP cyclohydrolase I (GTPCHI)...
  26. ncbi Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand recognition and mechanism of sulfonamide resistance
    Colin Levy
    Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
    Biochem J 412:379-88. 2008
    ..The results show that binding of DHPPP and pABA are separate distinguishable events in the reaction cycle, and that mutations which confer resistance to sulfonamide drugs act exclusively on the second step in the binding process...
  27. pmc 7-Substituted pterins provide a new direction for ricin A chain inhibitors
    Jeff M Pruet
    Department of Chemistry and Biochemistry, University of Texas at Austin, 1 University Station A1590, Austin, TX 78712, USA
    Eur J Med Chem 46:3608-15. 2011
    ..This makes the discovery of new inhibitors of great importance. We have previously used 6-substituted pterins, such as pteroic acid, as an inhibitor platform with moderate success...
  28. ncbi Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: crystallographic studies
    Jaroslaw Blaszczyk
    Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA
    Biochemistry 42:1573-80. 2003
    ..Two oxidized forms of HP are observed with an occupancy ratio of 0.50:0.50 in the 0.89-A structure. The oxidation of HP has significant impact on its binding to the protein as well as the conformation of nearby residue W89...
  29. ncbi Mutagenesis of folylpolyglutamate synthetase indicates that dihydropteroate and tetrahydrofolate bind to the same site
    Yi Sheng
    Department of Medical Genetics and Microbiology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada M5S 1A8
    Biochemistry 47:2388-96. 2008
    ..This suggests that the 5,10-methylenetetrahydrofolate binding site identified in the L. casei ternary structure may bind diglutamate and polyglutamate folate derivatives...
  30. ncbi Escherichia coli FolC structure reveals an unexpected dihydrofolate binding site providing an attractive target for anti-microbial therapy
    Magali Mathieu
    Department of Structural Biology, Aventis Pharma, 13 Quai J Guesde, F 94403 Vitry Seine, France
    J Biol Chem 280:18916-22. 2005
    ..As such, the presence of a folate binding site in E. coli FolC, which is different from the one seen in FPGS enzymes, provides avenues for the design of specific inhibitors of this enzyme in antimicrobial therapy...
  31. ncbi Oxidative stress in vitiligo: photo-oxidation of pterins produces H(2)O(2) and pterin-6-carboxylic acid
    Hartmut Rokos
    Institute for Pigmentary Disorders in Association with Ernst Moritz Arndt University, Greifswald, Germany
    Biochem Biophys Res Commun 292:805-11. 2002
    ....
  32. pmc Functional identification of orthologous genes encoding pterin recycling activity in Plasmodium falciparum and Toxoplasma gondii
    Qi Wang
    Faculty of Life Sciences, University of Manchester, Jackson s Mill, P O Box 88, Manchester M60 1QD, United Kingdom
    Mol Biochem Parasitol 146:109-12. 2006
  33. ncbi Mechanism of photooxidation of folic acid sensitized by unconjugated pterins
    M Laura Dantola
    INIFTA, Departamento de Quimica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata CONICET C C 16, Suc 4, 1900, La Plata, Argentina
    Photochem Photobiol Sci 9:1604-12. 2010
    ..This process also takes place with other pterins as photosensitizers...
  34. pmc Purification, overproduction, and partial characterization of beta-RFAP synthase, a key enzyme in the methanopterin biosynthesis pathway
    Joseph W Scott
    Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611 0700, USA
    J Bacteriol 184:4442-8. 2002
    ..extorquens is the first report of a putative methanopterin biosynthetic gene found in the Bacteria and provides evidence that the pathways of methanopterin biosynthesis in Bacteria and Archaea are similar...
  35. ncbi The mob locus of Escherichia coli K12 required for molybdenum cofactor biosynthesis is expressed at very low levels
    C Iobbi-Nivol
    Department of Biochemistry, Medical Sciences Institute, Dundee University, UK
    Microbiology 141:1663-71. 1995
    ..The mobB gene encodes a polypeptide with a putative nucleotide binding site. All available mob mutations which have been selected for by their ability to grow anaerobically in the presence of chlorate are located in the mobA gene...
  36. ncbi The crystal structure of the Escherichia coli MobA protein provides insight into molybdopterin guanine dinucleotide biosynthesis
    M W Lake
    Department of Biochemistry and Center for Structural Biology, State University of New York at Stony Brook, Stony Brook, New York 11794 5215, USA
    J Biol Chem 275:40211-7. 2000
    ..The binding site for MPT is located adjacent to the GTP-binding site in the C-terminal half of the molecule, which contains another set of conserved residues presumably involved in MPT binding...
  37. ncbi Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action
    A M Baca
    Department of Bioengineering and Biomolecular Structure Center, University of Washington, Seattle, WA 98195, USA
    J Mol Biol 302:1193-212. 2000
    ..Finally, the Mtb DHPS structure reveals a highly conserved pterin binding pocket that may be exploited for the design of novel antimycobacterial agents...
  38. ncbi Photosensitization of singlet oxygen formation by pterins and flavins. Time-resolved studies of oxygen phosphorescence under laser excitation
    S Y Egorov
    Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, 117021, Russia
    Biochemistry (Mosc) 64:1117-21. 1999
    ..of photosensitized 1O2 phosphorescence (1270 nm) were performed in air-saturated aqueous ((D2)O) solutions of pterins (2-amino-4-hydroxy-6,7-dimethylpteridine (DMP) and 2-amino-4-hydroxy-6-tetrahydroxybutyl-(D-arabo)pteridine (TOP))..
  39. ncbi Structural characteristics of methanogenic cofactors in the non-methanogenic archaebacterium Archaeoglobus fulgidus
    L G Gorris
    Department of Microbiology, Faculty of Science, University of Nijmegen, The Netherlands
    Biofactors 3:29-35. 1991
    ..The levels of the various cofactors were determined in cultures grown either on formate or lactate as the carbon source and sulphate or thiosulphate as the sulphur source...
  40. pmc Purine biosynthesis in the domain Archaea without folates or modified folates
    R H White
    Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg 24061 0308, USA
    J Bacteriol 179:3374-7. 1997
    ..It is concluded that archaea, which function with modified folates such as MPT, are able to carry out purine biosynthesis without the involvement of folates or modified folates...
  41. pmc An atypical orthologue of 6-pyruvoyltetrahydropterin synthase can provide the missing link in the folate biosynthesis pathway of malaria parasites
    Sabine Dittrich
    Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK
    Mol Microbiol 67:609-18. 2008
    ....
  42. ncbi Molybdenum cofactor biosynthesis in Escherichia coli. Requirement of the chlB gene product for the formation of molybdopterin guanine dinucleotide
    J L Johnson
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710
    J Biol Chem 266:12140-5. 1991
    ..Wild type cells were shown to contain both molybdopterin and molybdopterin guanine dinucleotide, while cells of chlB mutants were found to contain elevated levels of molybdopterin but no detectable molybdopterin guanine dinucleotide...
  43. pmc Molybdate and regulation of mod (molybdate transport), fdhF, and hyc (formate hydrogenlyase) operons in Escherichia coli
    J K Rosentel
    Department of Microbiology and Cell Science, University of Florida, Gainesville 32611, USA
    J Bacteriol 177:4857-64. 1995
    ..Upon entering the cytoplasm, molybdate branches out to mod regulation, fdhF and hyc activation, and metabolic conversion, leading to MGD synthesis and active molybdoenzyme synthesis...
  44. ncbi Crystal structure of 7,8-dihydropteroate synthase from Bacillus anthracis: mechanism and novel inhibitor design
    Kerim Babaoglu
    Department of Structural Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Structure 12:1705-17. 2004
    ..Finally, as an initial step in the development of pterin-based inhibitors, we present the structure of DHPS complexed with 5-nitro-6-methylamino-isocytosine...
  45. pmc Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency
    C J Meininger
    Cardiovascular Research Institute and Department of Medical Physiology, The Texas A and M University System Health Science Center, College Station, TX 77843 1114, USA
    Biochem J 349:353-6. 2000
    ..GTP-cyclohydrolase activity was low because of a decreased expression of the protein in the diabetic cells...
  46. pmc Pterin and folate salvage. Plants and Escherichia coli lack capacity to reduce oxidized pterins
    Alexandre Noiriel
    Horticultural Sciences Department, University of Florida, Gainesville, Florida 32611, USA
    Plant Physiol 143:1101-9. 2007
    ..In trypanosomatid parasites, reduction of such oxidized pterins is crucial for pterin and folate salvage. We therefore sought evidence for this reaction in plants...
  47. ncbi Plasma cytokine concentration changes induced by the antitumor agents dipterinyl calcium pentahydrate (DCP) and related calcium pterins
    Phillip Moheno
    SanRx Pharmaceuticals, Inc, La Jolla, CA 92037 8032, USA
    Immunobiology 214:135-41. 2009
    ..The finding that the novel calcium pterins and CaCl(2)...
  48. ncbi Thiocarboxylation of molybdopterin synthase provides evidence for the mechanism of dithiolene formation in metal-binding pterins
    G Gutzke
    Botanical Institute, Technical University of Braunschweig, 38023 Braunschweig, Germany
    J Biol Chem 276:36268-74. 2001
    ..A two-step reaction of MPT synthesis is proposed where the dithiolene is generated by two thiocarboxylates derived from a single tetrameric MPT synthase...
  49. ncbi Inhibition of GTP cyclohydrolase I by pterins
    R S Shen
    Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550
    Biochim Biophys Acta 965:9-15. 1988
    b>Pterins inhibit rat liver GTP cyclohydrolase I activity noncompetitively...
  50. ncbi Nitric oxide production and regulation of neuronal NOS in tyrosine hydroxylase containing neurons
    Qing Xu
    Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA
    Exp Neurol 188:341-50. 2004
    ..However, NO was not the primary mediator of cell death since NOS inhibitors rescued only less than 10% of the cells. These data suggest that endogenous NO production by nNOS is not a major factor in CAD cell death under these conditions...
  51. ncbi Possible impact of tetrahydrobiopterin and sepiapterin on endothelial dysfunction
    Nenad Blau
    Arterioscler Thromb Vasc Biol 23:913-4; author reply 914-5. 2003
  52. ncbi The autoxidation of tetrahydrobiopterin revisited. Proof of superoxide formation from reaction of tetrahydrobiopterin with molecular oxygen
    Michael Kirsch
    Institut fur Physiologische Chemie, Universitatsklinikum, Hufelandstrasse 55, D 45122 Essen, Germany
    J Biol Chem 278:24481-90. 2003
    ..Conclusively, because H4B can per se induce oxidative stress, an in vivo overproduction of this pterin, as is evident in various diseases, may be responsible for the observed acceleration of pathophysiological pathways...
  53. pmc A widespread riboswitch candidate that controls bacterial genes involved in molybdenum cofactor and tungsten cofactor metabolism
    Elizabeth E Regulski
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Mol Microbiol 68:918-32. 2008
    ..Furthermore, we identify variants of this RNA that are likely to be triggered by the related tungsten cofactor (Tuco), which carries tungsten in place of molybdenum as the metal constituent...
  54. ncbi D-threo-tetrahydrobiopterin is synthesized via 1'-oxo-2'-D-hydroxypropyl-tetrahydropterin in Dictyostelium discoideum Ax2
    Yong Kee Choi
    School of Biotechnology and Biomedical Science, Inje University, Kimhae 621 749, Korea
    FEBS Lett 579:3085-9. 2005
    ..These results are clear demonstration of the in vivo synthesis of DH4 via 1'-oxo-2'-D-hydroxypropyl-H4-pterin as well as an alternative synthesis of BH4 and DH4 in the complete absence of SR...
  55. ncbi Tetrahydrobiopterin precursor sepiapterin provides protection against neurotoxicity of 1-methyl-4-phenylpyridinium in nigral slice cultures
    Jakob Torp Madsen
    Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Odense, Denmark
    J Neurochem 85:214-23. 2003
    ..Accordingly, increasing intracellular tetrahydrobiopterin levels may protect against oxidative stress by complex-I inhibition...
  56. pmc Reduction and oxidation of the active site iron in tyrosine hydroxylase: kinetics and specificity
    Patrick A Frantom
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843, USA
    Biochemistry 45:2372-9. 2006
    ....
  57. ncbi Structure of tetrahydrobiopterin tunes its electron transfer to the heme-dioxy intermediate in nitric oxide synthase
    Chin Chuan Wei
    Department of Immunology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Biochemistry 42:1969-77. 2003
    ..4) Faster electron transfer from 5-methyl-H(4)B may be due to increased radical stability afforded by the N-5 methyl group...
  58. ncbi Specific interaction of the diastereomers 7(R)- and 7(S)-tetrahydrobiopterin with phenylalanine hydroxylase: implications for understanding primapterinuria and vitiligo
    Angel L Pey
    Department of Biomedicine, University of Bergen, Bergen, Norway
    FASEB J 20:2130-2. 2006
    ..Taken together, our results identified structural determinants for the specific regulation of PAH and TH by 7(S)BH4, which in turn aid in the understanding of primapterinuria and acute vitiligo...
  59. ncbi Order of substrate binding in bacterial phenylalanine hydroxylase and its mechanistic implication for pterin-dependent oxygenases
    Alon Volner
    Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, CA 90095 1569, USA
    J Biol Inorg Chem 8:121-8. 2003
    ..This represents the first conclusive steady-state mechanism for a PAH enzyme...
  60. ncbi Developmental regulation of neurotransmitter phenotype through tetrahydrobiopterin
    Beth A Habecker
    Department of Physiology and Pharmacology, Oregon Health and Sciences University School of Medicine, Portland, Oregon 97239, USA
    J Neurosci 22:9445-52. 2002
    ..These data also indicate that GCH expression, which is often coordinately regulated with TH expression, can be controlled independently of TH during development...
  61. ncbi Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidants
    Jeannette Vasquez-Vivar
    Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, USA
    Arterioscler Thromb Vasc Biol 22:1655-61. 2002
    ..The purpose of this study was to investigate the effects of hyperlipidemia on vascular BH4 levels and the effect of supplementation with sepiapterin in the presence and absence of N-acetylcysteine (NAC)...
  62. ncbi Function of MoaB proteins in the biosynthesis of the molybdenum and tungsten cofactors
    Loes E Bevers
    Department of Biotechnology, Delft University of Technology, Delft, The Netherlands
    Biochemistry 47:949-56. 2008
    ..coli MoaB is inactive. In summary, MogA, Cnx1G, and MoaB proteins exhibit the same adenylyl transfer activity essential for metal insertion in W or Mo cofactor maturation...
  63. ncbi The pteridine pathway in zebrafish: regulation and specification during the determination of neural crest cell-fate
    Irmgard Ziegler
    GSF Institut für Klinische Molekularbiologie und Tumorgenetik, Munchen, Germany
    Pigment Cell Res 16:172-82. 2003
    ....
  64. ncbi Fluorescence of pterin, 6-formylpterin, 6-carboxypterin and folic acid in aqueous solution: pH effects
    Andrés H Thomas
    Instituto de Investigaciones Fisicoquímica Teóricas y Aplicadas INIFTA, Universidad Nacional de La Plata, Casilla de Correo 16, Sucursal 4 1900 La Plata, Argentina
    Photochem Photobiol Sci 1:421-6. 2002
    ..Most pterins can exist in two acid-base forms over the pH range between 3 and 13...
  65. ncbi Tetrahydrobiopterin stimulates L-DOPA release from striatal tissue
    P Abreu-Gonzalez
    Department of Physiology, University of La Laguna 38320 Tenerife, Spain
    Eur J Pharmacol 541:33-7. 2006
    ..In summary 6-MPH4 stimulates L-DOPA release from striatal fragments incubated in vitro by a mechanism which involves NO or other free radicals derived from NO but not peroxynitrite...
  66. ncbi Homocysteine induces oxidative stress by uncoupling of NO synthase activity through reduction of tetrahydrobiopterin
    Gokce Topal
    Département de Signalisation cellulaire et athérosclérose précoce, UMR CNRS 7131 Université Paris 6, Hopital Broussais, 102 rue Didot, 75014 Paris, France
    Free Radic Biol Med 36:1532-41. 2004
    ..The results show that the oxidative stress and inhibition of NO release induced by homocysteine depend on eNOS uncoupling due to reduction of intracellular tetrahydrobiopterin availability...
  67. ncbi Thermodynamic characterization of the binding of tetrahydropterins to phenylalanine hydroxylase
    Angel Luis Pey
    Contribution from the Centro de Biología Molecular Severo Ochoa, CSIC UniversidadAutónoma de Madrid, 28049 Madrid, Spain
    J Am Chem Soc 126:13670-8. 2004
    ..No significant changes in binding affinity were observed in the 5-35 degrees C temperature range for both pterins at neutral pH, but the enthalpic contribution increased with temperature rendering a heat capacity change (..
  68. ncbi Sepiapterin decreases vasorelaxation in nitric oxide synthase inhibition-induced hypertension
    Brett M Mitchell
    Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912, USA
    J Cardiovasc Pharmacol 43:93-8. 2004
    ..These results support the hypothesis that sepiapterin further reduces vasodilation in the presence of NOS inhibition and may be caused by BH4 autoxidation...
  69. pmc Catalytic reduction of a tetrahydrobiopterin radical within nitric-oxide synthase
    Chin Chuan Wei
    Department of Pathobiology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 283:11734-42. 2008
    ..These results, in light of existing NOS crystal structures, suggest a "through-heme" mechanism may operate for H(4)B radical reduction in NOS...
  70. ncbi Redox reactions of the pyranopterin system of the molybdenum cofactor
    Sharon J Nieter Burgmayer
    Department of Chemistry, Bryn Mawr College, Bryn Mawr, PA 19010, USA
    J Biol Inorg Chem 9:59-66. 2004
    ..The work presented here has important implications for understanding the biosynthesis and reaction chemistry of the pyranopterin cofactor in molybdenum and tungsten enzymes...
  71. ncbi Ability of tetrahydrobiopterin analogues to support catalysis by inducible nitric oxide synthase: formation of a pterin radical is required for enzyme activity
    Amy R Hurshman
    Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 42:13287-303. 2003
    ..Although binding of H(4)B also stabilizes the NOS structure and active site, the most critical role of the pterin cofactor in NOS appears to be in electron transfer...
  72. ncbi Ascorbate enhances iNOS activity by increasing tetrahydrobiopterin in RAW 264.7 cells
    Kozo Nakai
    Department of Dermatology, Kagawa Medical University, Kagawa, Japan
    Free Radic Biol Med 35:929-37. 2003
    ..These data suggest that enhanced activation of iNOS by ascorbic acid is mediated by increasing the stability of BH4 in RAW 264.7 cells...
  73. ncbi In vitro molybdenum ligation to molybdopterin using purified components
    Jason D Nichols
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:7817-22. 2005
    ..This effect was not observed in the absence of MoeA. The results presented here demonstrate that MoeA is responsible for mediating molybdenum ligation to molybdopterin, whereas MogA stimulates this activity in an ATP-dependent manner...
  74. pmc Acute inhibition of guanosine triphosphate cyclohydrolase 1 uncouples endothelial nitric oxide synthase and elevates blood pressure
    Shuangxi Wang
    Department of Medicine, Division of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Hypertension 52:484-90. 2008
    ..In conclusion, GTPCH1 via BH4 maintains normal BP and endothelial function in vivo by preserving NO synthesis by eNOS...
  75. pmc Tetrahydrobiopterin prevents platelet-activating factor-induced intestinal hypoperfusion and necrosis: Role of neuronal nitric oxide synthase
    Xiao Wu Qu
    Department of Pathology, Children s Memorial Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    Crit Care Med 33:1050-6. 2005
    ..Here, we investigated whether intestinal perfusion is regulated by nNOS and whether tetrahydrobiopterin, a co-factor and stabilizer of nNOS, reverses PAF-induced intestinal hypoperfusion and injury...
  76. ncbi Physarum polycephalum expresses a dihydropteridine reductase with selectivity for pterin substrates with a 6-(1', 2'-dihydroxypropyl) substitution
    Claudia Wild
    Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Str 3, A 6020 Innsbruck, Austria
    Biol Chem 384:1057-62. 2003
    ..Our results demonstrate that Physarum synthesizes, utilizes and metabolizes tetrahydrobiopterin in a way hitherto thought to be restricted to the animal kingdom...
  77. ncbi Lack of nitric oxide mediation of flow-dependent arteriolar dilation in type I diabetes is restored by sepiapterin
    Zsolt Bagi
    Department of Pathophysiology, Semmelweis University, Budapest, Hungary
    J Vasc Res 40:47-57. 2003
    ....
  78. ncbi Syntheses of labeled vitamers of folic acid to be used as internal standards in stable isotope dilution assays
    Achim Freisleben
    Institut für Lebensmittelchemie der Technischen Universität München, Lichtenbergstrasse 4, D 85748 Garching, Germany
    J Agric Food Chem 50:4760-8. 2002
    ..The mass spectrometric studies confirmed that the compounds could be used as internal standards in stable isotope dilution assays...
  79. ncbi Pteridine derivatives as modulators of oxidative stress
    K Oettl
    Institute of Medical Chemistry and Pregl Laboratory, Karl Franzens University Graz, Austria
    Curr Drug Metab 3:203-9. 2002
    ..The general view during the initial phase of investigations on this special field was, that reduced pterins, i. e...
  80. ncbi Reconstitution of pterin-free inducible nitric-oxide synthase
    K M Rusche
    Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan 48109-0606, USA
    J Biol Chem 276:421-7. 2001
    ..Apparent binding constants were determined for the 6-methyl- (50 microm) and 6-ethoxymethyl (200 microm) deazapterins. The redox-stable pterin analogs appear to bind to NOS in a different manner than H(4)B...
  81. ncbi Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II
    Kengo Fujimoto
    Department of Biochemistry, Meikai University School of Dentistry, Sakado, Saitama 350 0283, Japan
    Biochim Biophys Acta 1594:191-8. 2002
    ..We also recognized that only Ser-213 of human SPR was phosphorylated. Each of these serine residues in SPR was found in the consensus sequence (Arg-X-X-Ser/Thr) of the phosphorylation site...
  82. ncbi Bacterial lipopolysaccharide down-regulates expression of GTP cyclohydrolase I feedback regulatory protein
    Ernst R Werner
    Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Strasse 3, A 6020 Innsbruck, Austria
    J Biol Chem 277:10129-33. 2002
    ..These results demonstrate that LPS down-regulates expression of GFRP, thus rendering pteridine synthesis independent of metabolic control by phenylalanine...
  83. ncbi A comparative study of Drosophila phenylalanine hydroxylase with a natural and a synthetic tetrahydropterin as cofactor
    Y Bel
    Departamento de Genetica, Facultad de Biologia, Universitat de Valencia, Spain
    Comp Biochem Physiol B 103:557-62. 1992
    ..This inhibition did not happen with H4Bip. The presence of the pteridine 7-xanthopterin in adult bodies was not the cause of this inhibition...
  84. pmc Effects of sepiapterin and 6-acetyldihydrohomopterin on the guanosine triphosphate cyclohydrolase I of mouse, rat and the fruit-fly Drosophila
    K B Jacobson
    Biology Division, Oak Ridge National Laboratory, TN 37831
    Biochem J 260:135-41. 1989
    ..These studies demonstrate that micromolar levels of reduced pterins may have regulatory effects on GTP cyclohydrolase I and that a mouse mutant is available that has low enough ..
  85. ncbi Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin
    J B Laursen
    Department of Medicine, Emory University School of Medicine, and Veterans Administration Hospital, Atlanta, GA 30322, USA
    Circulation 103:1282-8. 2001
    ..Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase...
  86. pmc Pterin interactions with distinct reductase activities of NO synthase
    M M Pantke
    Department of Pharmacology and Toxicology, , Versbacher Str. 9, , Germany
    Biochem J 356:43-51. 2001
    ..However, occupation of an exosite near the pterin site in NOS by type II anti-pterins may interfere with the electron flow within the active centre, suggesting that steric perturbation of the pterin ..
  87. pmc Control of 6-(D-threo-1',2'-dihydroxypropyl) pterin (dictyopterin) synthesis during aggregation of Dictyostelium discoideum. Involvement of the G-protein-linked signalling pathway in the regulation of GTP cyclohydrolase I activity
    M Gutlich
    GSF Institut für Klinische Molekularbiologie und Tumorgenetik, Munchen, Germany
    Biochem J 314:95-101. 1996
    ..discoideum...
  88. ncbi Mechanism of suppression in Drosophila: control of sepiapterin synthase at the purple locus
    J J Yim
    Science 198:1168-70. 1977
    ..We hypothesize that the purple locus may be a structural gene for sepiapterin synthase in Drosophila...
  89. ncbi Interleukin-1beta-induced nitric oxide production and inhibition of insulin secretion in rat islets of langerhans is dependent upon the nitric oxide synthase cofactor tetrahidrobiopterin
    P Stickings
    University of Brighton, School of Pharmacy and Biomolecular Sciences, Cockcroft Building, Moulsecoomb, Brighton, BN2 4GJ, UK
    Cytokine 18:81-5. 2002
    ..While a contribution of non-NO mediators cannot be excluded, our results support the proposal that IL-1 beta-induced, NO-mediated inhibition of insulin secretion in rat islets is dependent on the NOS cofactor BH(4)...
  90. ncbi Glutathione depletion in nigrostriatal slice cultures: GABA loss, dopamine resistance and protection by the tetrahydrobiopterin precursor sepiapterin
    Jan Bert Gramsbergen
    Anatomy and Neurobiology, Institute of Medical Biology, SDU Odense University, Winsloewparken 21, DK 5000 C Odense, Denmark
    Brain Res 935:47-58. 2002
    ..We suggest that under pathological conditions with reduced GSH, impaired synthesis of BH(4) may accelerate nigral cell loss, whereas increasing intracellular BH(4) may provide protection to both DA and GABA neurons...
  91. ncbi Anti-inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: modulation of inducible nitric oxide synthase
    Albert Huisman
    Department of Vascular Medicine, University Medical Center, Utrecht, The Netherlands
    FASEB J 16:1135-7. 2002
    ..Our findings support the hypothesis that BH4 can be used to modulate the function of the inflammatory iNOS isoform and suggest a potential therapeutic role for sepiapterin in early allograft rejection...
  92. ncbi Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP
    G Werner-Felmayer
    Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria
    J Biol Chem 268:1842-6. 1993
    ..Thus, cytokines indirectly stimulate the activity of constitutive NO synthase in HUVEC by upregulating production of the cofactor tetrahydrobiopterin...
  93. ncbi Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center
    C S Raman
    Department of Molecular Biology and Biochemistry, University of California, Irvine 92697 3900, USA
    Cell 95:939-50. 1998
    ..The unexpected recognition of the substrate, L-arginine, at the H4B site indicates that this site is poised to stabilize a positively charged pterin ring and suggests a model involving a cationic pterin radical in the catalytic cycle...
  94. pmc Production of sepiapterin in Escherichia coli by coexpression of cyanobacterial GTP cyclohydrolase I and human 6-pyruvoyltetrahydropterin synthase
    Hyun Joo Woo
    Department of Microbiology, Inje University, Kimhae 621 749, Korea
    Appl Environ Microbiol 68:3138-40. 2002
    ..Aldose reductase, another indispensable enzyme for sepiapterin production, may be endogenous in E. coli...
  95. ncbi Enzymatic conversion of dihydroneopterin triphosphate to the pyrimidodiazepine intermediate involved in the biosynthesis of the drosopterins in Drosophila melanogaster
    G J Wiederrecht
    J Biol Chem 259:2195-200. 1984
    ..Oxidized glutathione cannot replace reduced glutathione in the system. The yield of PDA produced enzymatically from H2-NTP can be as high as 40% under optimal conditions...
  96. pmc High-resolution structures of the bifunctional enzyme and transcriptional coactivator DCoH and its complex with a product analogue
    J D Cronk
    Department of Molecular and Cell Biology, University of California at Berkeley 94720 3206, USA
    Protein Sci 5:1963-72. 1996
    ..The dihedral symmetry of DCoH suggests that binding to the dimerization domain of HNF-1 likely involves the superposition of two-fold rotation axes of the two proteins...
  97. ncbi Disorders of biopterin metabolism
    Nicola Longo
    Division of Medical Genetics, Department of Pediatrics and Pathology, University of Utah, 2C 412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132, USA
    J Inherit Metab Dis 32:333-42. 2009
    ..the measurement of pterin metabolites in urine, dihydropteridine reductase in blood spots, neurotransmitters and pterins in the CSF and on the demonstration of reduced enzyme activity (red blood cells or fibroblasts) or causative ..
  98. pmc On the origin of biochemistry at an alkaline hydrothermal vent
    William Martin
    Institute of Botany, University of Dusseldorf, 40225 Dusseldorf, Germany
    Philos Trans R Soc Lond B Biol Sci 362:1887-925. 2007
    ..The synthesis of formyl pterins, which are essential intermediates of the Wood-Ljungdahl pathway and purine biosynthesis, is found to confront ..
  99. ncbi Behavioral mutants of Euglena gracilis: functional and spectroscopic characterization
    M Lebert
    Institut fur Botanik und Pharmazeutische Biologie, Friedrich Alexander Universitat, Erlangen, Germany
    J Plant Physiol 151:188-95. 1997
    ..Using the fluorescence of the chromophoric groups believed to be involved in photoperception (flavins and pterins) a method was developed for an in situ and in vivo detection of the paraxonemal body, the proposed location of ..
  100. ncbi Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia
    Nico G Abeling
    Academic Medical Center, Laboratory Genetic Metabolic Diseases, University of Amsterdam, Amsterdam, The Netherlands
    Mol Genet Metab 89:116-20. 2006
    ..The diagnostic approach with CSF neurotransmitter and pterins analysis and combined phenylalanine/BH(4) loading test, and finally measurement of sepiapterin in CSF is ..
  101. ncbi Tetrahydrobiopterin prevents nitration of tyrosine hydroxylase by peroxynitrite and nitrogen dioxide
    Donald M Kuhn
    Wayne State University School of Medicine, 2125 Scott Hall, 540 E Canfield, Detroit, MI 48201, USA
    Mol Pharmacol 64:946-53. 2003
    ..Reduced pterins prevent neither the inhibition of TH activity nor cysteine modification caused by peroxynitrite or NO2, despite ..

Research Grants25

  1. SPECTROSCOPIC AND MECHANISTIC STUDIES OF HEME ENZYMES
    Ryan Kinloch; Fiscal Year: 2007
    ..catalysis of nitric oxide synthase (NOS) by conducting single and double mixing experiments with six different pterins and three different substrates...
  2. BIOCHEMISTRY OF NITRIC OXIDE SYNTHESIS
    Dennis J Stuehr; Fiscal Year: 2010
    ..Aim 2. Investigate redox-independent effects of pterins on the reduction, stability, and subsequent reactivity of the FeII02 intermediate in NOS...
  3. BIOINORGANIC COPPER COORDINATION CHEMISTRY
    KENNETH KARLIN; Fiscal Year: 2002
    ..Chelating pterins will be used to study Cu/O2 reactions with reduced pterins and substrates...
  4. CRYSTALLOGRPHIC ANALYSIS OF DRUG TARGET ENZYMES
    Jon Robertus; Fiscal Year: 2000
    ..of alternative heterocyclic analogs; these should make stronger interactions with the target enzyme than do the pterins. Pendant groups will be attached to make specific contacts to a second binding site identified on the enzyme...
  5. CIRCULATORY SHOCK, NITRIC OXIDE AND TETRAHYDROBIOPTERIN
    Steven Gross; Fiscal Year: 2003
    ..balance BH4 with cellular needs; 3) to characterize processes that mediate cellular uptake and efflux of reduced pterins and the contribution of pterin transport to regulation of BH4 levels in vascular smooth muscle; 4) to elucidate ..
  6. Molybdenum Pterin-Dithiolene Complexes for Model Studies of the Catalytic Site of
    SHARON BURGMAYER; Fiscal Year: 2007
    ..pterin-dithiolene by chemical and electrochemical methods; (b) to probe the electronic effects of pterins at different levels of reduction on the Mo-dithiolene unit; (c) to accomplish full spectroscopic and structural ..
  7. Superoxide Generation from eNOS: The Role of Pterins
    JEANNETTE M VASQUEZ VIVAR; Fiscal Year: 2010
    ..Generally this proposal is aimed at understanding these fundamental mechanisms that should provide the basis for developing new and improved strategies in the prevention and treatment of atherosclerosis and CVD. ..
  8. Tetrahydrobiopterin in Hypoxia-Ischemia Induced Fetal Brain Dysfunction
    Jeannette Vasquez Vivar; Fiscal Year: 2008
    ..This information will likely define the use of tetrahydrobiopterin in the prevention and/or amelioration of H-I induced fetal brain dysfunction, which remains a major medical challenge. [unreadable] [unreadable] [unreadable]..
  9. NOVEL APPROACHES TO ANTIFOLATE CHEMOTHERAPY
    Andre Rosowsky; Fiscal Year: 2003
    ..The focus will be on enhancing polyglutamation of the lead compound dmAMT by modification of the B-ring and/or pABA moiety. ..
  10. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 2004
    ..Analogs of PT653 with a COOH, NH2, or OH group on the tricyclic moiety, and prodrugs thereof, will be made with the goal of improving aqueous solubility without sacrificing potency or selectivity. ..
  11. Anaplerotic therapy in Propionic Acidemia
    Nicola Longo; Fiscal Year: 2008
    ..This approach, if effective, could be extended to a number of other diseases, including other organic acidemias and mitochondrial disorders. [unreadable] [unreadable] [unreadable]..
  12. iNOS Posttranslational Regulation in Cardiac Rejection
    GALEN PIEPER; Fiscal Year: 2009
    ..A better understanding of this molecular process may lead to better strategies to prevent injury cardiac cells in these patients. ..
  13. Methamphetamine Neurotoxicity and Microglial Activation
    DONALD KUHN; Fiscal Year: 2009
    ..A better understanding of the mechanisms by which METH causes persistent damage to the DA neuronal system could lead to more targeted therapies and would open newer lines of investigation into this and other neurotoxic drugs of abuse. ..
  14. THE CARNITINE TRANSPORTER IN HUMAN DISEASE
    Nicola Longo; Fiscal Year: 2010
    ....
  15. Molecular Neurobiology of Drug Abuse
    DONALD KUHN; Fiscal Year: 2006
    ..Kuhn will remain extensively engaged in scientific mentoring activities. ..
  16. Oxidative Stress and Pteridine Metabolism in Diabetes
    Cynthia Meininger; Fiscal Year: 2005
    ..abstract_text> ..
  17. NEUROSCIENCE TRAINING IN DRUG ABUSE
    DONALD KUHN; Fiscal Year: 2004
    ..abstract_text> ..
  18. MOLECULAR TARGETS OF NITRIC OXIDE IN CARDIAC TRANSPLANTS
    GALEN PIEPER; Fiscal Year: 2004
    ..These studies will provide a novel mechanism to explain the pathogenesis of dyskinesis and graft failure during cardiac transplant rejection. ..
  19. PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
    DONALD KUHN; Fiscal Year: 2002
    ....
  20. MICROARRAY ANALYSIS OF HUMAN COCAINE ADDICTS
    DONALD KUHN; Fiscal Year: 2002
    ..Microarray-based scanning of the human genome has the potential to establish those genes or gene clusters that define the addictive phenotype, leading the way to proteomic-based studies of the bases of addiction. ..
  21. MODEL STUDIES OF LOW BARRIER HYDROGEN BONDS IN CATALYSIS
    Eric Anslyn; Fiscal Year: 2001
    ..The significance of such a result goes beyond an increased basic science understanding of enzymology, and has clear ramifications in the design of synthetic catalysts for biomedical and synthetic applications. ..
  22. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2010
    ..These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilitiesin the structure-based correlations to help design novel pjDHFRinhibitors. ..