Design and synthesis of chromogenic thiopeptolide substrates as MetAPs active site probes

Bioorg Med Chem. 2004 Jun 1;12(11):2853-61. doi: 10.1016/j.bmc.2004.03.044.

Abstract

Twenty one chromogenic thiopeptolide substrates were designed and synthesized as the active site probes and analyzed with each S1 site of mutant residues and enzymes of wild-type MetAP1s. The preliminary enzymatic experiments indicate that cysteine 70 or 202, at either Escherichia coli or human MetAP1, played a crucial role in the methionine hydrolysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Aminopeptidases / chemistry*
  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism*
  • Animals
  • Binding Sites
  • Chromogenic Compounds / chemical synthesis*
  • Chromogenic Compounds / chemistry
  • Chromogenic Compounds / metabolism*
  • Cyclosporins / chemical synthesis
  • Cyclosporins / chemistry
  • Cyclosporins / metabolism
  • Escherichia coli / enzymology
  • Humans
  • Hydrolysis
  • Methionine / metabolism*
  • Methionyl Aminopeptidases
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Point Mutation
  • Sulfhydryl Compounds / analysis

Substances

  • Chromogenic Compounds
  • Cyclosporins
  • Oligopeptides
  • Sulfhydryl Compounds
  • Methionine
  • Aminopeptidases
  • Methionyl Aminopeptidases