Abstract

The chemical synthesis and biological evaluation of """"""""transition-state analog"""""""" inhibitors for several group-transfer enzymes are being investigated. These compounds, all designed on the basis of detailed mechanistic studies of relevant enzymes, are to be used as biochemical and pharmacological probes, and have potential use in chemotherapy of various disease states.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028097-07
Application #
3167979
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1979-09-30
Project End
1986-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Rensselaer Polytechnic Institute
Department
Type
Schools of Arts and Sciences
DUNS #
002430742
City
Troy
State
NY
Country
United States
Zip Code
12180

  Publications

McGuire, John J; Bartley, David M; Tomsho, John W et al. (2009) Inhibition of human folylpolyglutamate synthetase by diastereomeric phosphinic acid mimics of the tetrahedral intermediate. Arch Biochem Biophys 488:140-5
Majumdar, Debatosh; Alexander, Matthew D; Coward, James K (2009) Synthesis of isopeptide epoxide peptidomimetics. J Org Chem 74:617-27
Coward, James K; McGuire, John J (2008) Mechanism-based inhibitors of folylpoly-gamma-glutamate synthetase and gamma-glutamyl hydrolase: control of folylpoly-gamma-glutamate homeostasis as a drug target. Vitam Horm 79:347-73
Tomsho, John W; Moran, Richard G; Coward, James K (2008) Concentration-dependent processivity of multiple glutamate ligations catalyzed by folylpoly-gamma-glutamate synthetase. Biochemistry 47:9040-50
Alexander, Jessica P; Ryan, Thomas J; Ballou, David P et al. (2008) Gamma-glutamyl hydrolase: kinetic characterization of isopeptide hydrolysis using fluorogenic substrates. Biochemistry 47:1228-39
Yang, Yonghong; Coward, James K (2007) Synthesis of p-aminophenyl aryl H-phosphinic acids and esters via cross-coupling reactions: elaboration to phosphinic acid pseudopeptide analogues of pteroyl glutamic acid and related antifolates. J Org Chem 72:5748-58
Bartley, David M; Coward, James K (2006) Regioselective synthesis of alpha-methyl 2-methyleneglutarate via a novel lactonization-elimination rearrangement. J Org Chem 71:372-4
Feng, Yan; Coward, James K (2006) Prodrug forms of N-[(4-deoxy-4-amino-10-methyl)pteroyl]glutamate-gamma-[psiP(O)(OH)]-glutarate, a potent inhibitor of folylpoly-gamma-glutamate synthetase: synthesis and hydrolytic stability. J Med Chem 49:770-88
Bartley, David M; Coward, James K (2005) A stereoselective synthesis of phosphinic acid phosphapeptides corresponding to glutamyl-gamma-glutamate and incorporation into potent inhibitors of folylpoly-gamma-glutamyl synthetase. J Org Chem 70:6757-74
Tomsho, John W; McGuire, John J; Coward, James K (2005) Synthesis of (6R)- and (6S)-5,10-dideazatetrahydrofolate oligo-gamma-glutamates: kinetics of multiple glutamate ligations catalyzed by folylpoly-gamma-glutamate synthetase. Org Biomol Chem 3:3388-98

Showing the most recent 10 out of 39 publications