Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase. Part 2: substitution of the glycine part

Bioorg Med Chem Lett. 2002 Oct 7;12(19):2703-5. doi: 10.1016/s0960-894x(02)00538-3.

Abstract

Glutathionylspermidine synthetase (GspS) is an essential enzyme in the biosynthesis of trypanothione and is an attractive target for the design of selective anti-parasitic drugs. We synthesised a series of analogues of glutathione (L-gamma-Glu-L-Leu-X) where the glycine moiety has been substituted for other amino acids. These peptides were evaluated as substrates and inhibitors of GspS. Compounds with basic side chains such as diaminopropionic acid were found to be good inhibitors (K(i): 7.2 microM). Substitution of the glycine part abolished the GspS substrate properties of the tripeptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amide Synthases / antagonists & inhibitors*
  • Amino Acid Substitution
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Glutathione / pharmacology*
  • Glycine / chemistry*
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology*

Substances

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