Synthesis of potent water-soluble tissue transglutaminase inhibitors

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5559-62. doi: 10.1016/j.bmcl.2008.09.006. Epub 2008 Sep 6.

Abstract

Dipeptide-based sulfonium peptidylmethylketones derived from 6-diazo-5-oxo-L-norleucine (DON) have been investigated as potential water-soluble inhibitors of extracellular transglutaminase. The lead compounds were prepared in four steps and exhibited potent activity against tissue transglutaminase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Chemistry, Pharmaceutical / methods
  • Diazooxonorleucine / chemistry*
  • Drug Design
  • Ethanol / chemistry
  • GTP-Binding Proteins / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Ketones / chemistry
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry / methods
  • Peptides / chemistry
  • Protein Glutamine gamma Glutamyltransferase 2
  • Solubility
  • Spectrophotometry / methods
  • Transglutaminases / antagonists & inhibitors*
  • Water / chemistry*

Substances

  • Ketones
  • Peptides
  • Diazooxonorleucine
  • Water
  • Ethanol
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins