Simple N(ε)-thioacetyl-lysine-containing cyclic peptides exhibiting highly potent sirtuin inhibition

Yajun Huang; Jiajia Liu; Lingling Yan; Weiping Zheng

doi:10.1016/j.bmcl.2016.01.086

Simple N(ε)-thioacetyl-lysine-containing cyclic peptides exhibiting highly potent sirtuin inhibition

Bioorg Med Chem Lett. 2016 Mar 15;26(6):1612-1617. doi: 10.1016/j.bmcl.2016.01.086. Epub 2016 Feb 1.

Authors

Yajun Huang¹, Jiajia Liu¹, Lingling Yan¹, Weiping Zheng²

Affiliations

¹ School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
² School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China. Electronic address: wzheng@ujs.edu.cn.

PMID: 26874402
DOI: 10.1016/j.bmcl.2016.01.086

Abstract

Transforming a linear pentapeptidic pan-SIRT1/2/3 inhibitor harboring the catalytic mechanism-based sirtuin inhibitory warhead N(ε)-thioacetyl-lysine into its side chain-to-side chain cyclized derivatives was able to furnish highly potent SIRT1/2/3 inhibition (low nM). This finding attests to the feasibility of developing structurally simple yet highly potent catalytic mechanism-based cyclic peptidic sirtuin inhibitors.

Keywords: Catalytic mechanism-based; Cyclic peptide; Inhibitor; Sirtuin.

Publication types

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

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Lysine / analogs & derivatives*
Lysine / chemistry
Lysine / pharmacology
Models, Molecular
Molecular Structure
Peptides, Cyclic / chemistry
Peptides, Cyclic / pharmacology*
Sirtuins / antagonists & inhibitors*
Sirtuins / metabolism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
N(epsilon)-thioacetyllysine
Peptides, Cyclic
Sirtuins
Lysine