A Selective Cyclic Peptidic Human SIRT5 Inhibitor.
In the current study, we discovered that a side chain-to-side chain cyclic pentapeptide harboring a central N(ε)-carboxyethyl-thiocarbamoyl-lysine residue behaved as a strong and selective (versus human SIRT1/2/3/6) inhibitor against human SIRT5-catalyzed deacylation reaction. This compound was also found to be proteolytically much more stable than its linear counterpart. This compound could be a valuable lead for developing stronger, selective, metabolically stable, and cell permeable human SIRT5 inhibitors.
School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, China. liujiajia2401@163.com.
Jiajia
J
Liu
School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, China. huangyajun0205@163.com.
Yajun
Y
Huang
School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, China. wzheng@ujs.edu.cn.
Weiping
W
Zheng
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; C508544:SIRT5 protein, human; D037761:Sirtuins
Nε-carboxyethyl-thiocarbamoyl-lysine; SIRT5; cyclic peptide; inhibitor; sirtuin