Jump to main content
Jump to site search

Issue 3, 2010
Previous Article Next Article

Discovery of potent, proteolytically stable, and cell permeable human sirtuin peptidomimetic inhibitors containing Nε-thioacetyl-lysine

Author affiliations

Abstract

Inhibitors of sirtuin-catalyzed NAD+-dependent protein lysine deacetylation reaction possess great value for facilitating deciphering the biology of sirtuins and as potential therapeutic agents for metabolic and age-related diseases and cancer. Built upon our previously discovered potent Nε-thioacetyl-lysine (ThAcK)-containing 18-amino acid peptidic human sirtuin inhibitor 1, we performed a structure–activity-relationship (SAR) study with the goal of transforming this potent peptidic inhibitor to potent yet proteolytically stable, cell permeable, and low molecular weight ThAcK-containing peptidomimetic inhibitors. Specifically, in this SAR study, we have identified two such peptidomimetic inhibitors (8 and 9) that exhibited potent in vitro and in vivo human sirtuin inhibition and whose molecular weights are in the 500 Da range.

Graphical abstract: Discovery of potent, proteolytically stable, and cell permeable human sirtuin peptidomimetic inhibitors containing Nε-thioacetyl-lysine

Back to tab navigation

Supplementary files

Article information


Submitted
25 Jun 2010
Accepted
29 Jul 2010
First published
18 Aug 2010

Med. Chem. Commun., 2010,1, 233-238
Article type
Concise Article

Discovery of potent, proteolytically stable, and cell permeable human sirtuin peptidomimetic inhibitors containing Nε-thioacetyl-lysine

B. M. Hirsch, C. A. Gallo, Z. Du, Z. Wang and W. Zheng, Med. Chem. Commun., 2010, 1, 233
DOI: 10.1039/C0MD00089B

Search articles by author

Spotlight

Advertisements