Multisubstrate adduct inhibitors of glycinamide ribonucleotide transformylase: Synthetic and enzyme-assembled.

James Inglese, Stephen J. Benkovic

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

β-TGDDF, the displacement product of 2-thioacetamide ribonucleotide and N-10-(bromoacetyl)-5,8-dideazafolate, is a potent, slow, tight-binding, multisubstrate adduct inhibitor (MAI) of glycinamide ribonucleotide transformylase (GAR TFase: E.C. 2.1.2.2.). The mechanism of inhibition by this MAI and its derivatives are reported. In addition, a related series of MAIs formed from the interaction of glycinamide ribonucleotide (GAR) or its carbocyclic analog (carbo-β-GAR) and N-10-(bromoacetyl)-5,8-dideazafol with GAR TFase have been discovered and characterized. These latter enzyme assembled inhibitors represent a novel route to the inhibition of GAR TFase.

Original languageEnglish (US)
Pages (from-to)2351-2364
Number of pages14
JournalTetrahedron
Volume47
Issue number14-15
DOIs
StatePublished - 1991

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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