Inhibitors of the chymotrypsin-like activity of proteasome based on di- and tri-peptidyl alpha-keto aldehydes (glyoxals)

J F Lynas; P Harriott; A Healy; M A McKervey; B Walker

doi:10.1016/s0960-894x(98)00030-4

Inhibitors of the chymotrypsin-like activity of proteasome based on di- and tri-peptidyl alpha-keto aldehydes (glyoxals)

Bioorg Med Chem Lett. 1998 Feb 17;8(4):373-8. doi: 10.1016/s0960-894x(98)00030-4.

Authors

J F Lynas¹, P Harriott, A Healy, M A McKervey, B Walker

Affiliation

¹ Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University Belfast, Northern Ireland, U.K.

PMID: 9871688
DOI: 10.1016/s0960-894x(98)00030-4

Abstract

A series of peptidyl alpha-keto aldehydes (glyoxals) have been synthesised as putative inhibitors of the chymotryptic-like activity of proteasome. The most potent peptides, Cbz-Leu-Leu-Tyr-COCHO and Bz-Leu-Leu-Leu-COCHO, function as slow-binding reversible inhibitors, exhibiting final Ki values of approximately 3.0 nM. These are among the lowest values so far reported for (tri)peptide-based aldehyde-related inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chymotrypsin / antagonists & inhibitors*
Cysteine Endopeptidases / blood
Cysteine Endopeptidases / drug effects*
Glyoxal / pharmacology*
Humans
Multienzyme Complexes / blood
Multienzyme Complexes / drug effects*
Proteasome Endopeptidase Complex
Trypsin Inhibitors / pharmacology*

Substances

Multienzyme Complexes
Trypsin Inhibitors
Glyoxal
Chymotrypsin
Cysteine Endopeptidases
Proteasome Endopeptidase Complex