Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 1: Substitution of the glycine carboxylic acid group

Bioorg Med Chem Lett. 2002 Sep 16;12(18):2553-6. doi: 10.1016/s0960-894x(02)00489-4.

Abstract

Glutathionylspermidine synthetase/amidase (GspS) is an essential enzyme in the biosynthesis and turnover of trypanothione and represents an attractive target for the design of selective anti-parasitic drugs. We synthesised a series of analogues of glutathione (L-gamma-Glu-L-Leu-Gly-X) where the glycine carboxylic acid group (X) has been substituted for other acidic groups such as tetrazole, hydroxamic acid, acylsulphonamide and boronic acid. The boronic acid appears the most promising lead compound (IC(50) of 17.2 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amide Synthases / antagonists & inhibitors*
  • Carboxylic Acids / chemistry*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glutathione / chemistry
  • Glutathione / pharmacology*
  • Glycine / chemistry*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*

Substances

  • Carboxylic Acids
  • Enzyme Inhibitors
  • Oligopeptides
  • Amide Synthases
  • glutathionylspermidine synthetase
  • Glutathione
  • Glycine