title: Cyclic peptide-based potent and selective SIRT1/2 dual inhibitors harboring Nε-thioacetyl-lysine.
abstract: In the current study, we discovered that several N-terminus-to-side chain cyclic tripeptides harboring the catalytic mechanism-based SIRT1/2/3 inhibitory warhead Nε-thioacetyl-lysine at their central positions exhibited a comparably strong inhibition (nM level) against the SIRT1/2-catalyzed Nε-acetyl-lysine deacetylation reactions. Their dual SIRT1/2 inhibitory action was also found to be stronger than that against SIRT3/5/6. Considering the previous demonstration that a SIRT1/2 dual inhibition could be instrumental in achieving an anti-cancer effect on those cancers retaining the wild-type tumor suppresser p53 protein, these compounds could be employed as leads for developing novel anti-cancer agents.
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China. Electronic address: wzheng@ujs.edu.cn.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000107:Acetylation; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors*; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors*
chemical_list: C513649:N(epsilon)-thioacetyllysine; D010456:Peptides, Cyclic; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D008239:Lysine
keywords: Cyclic peptide; Inhibitor; N(ε)-thioacetyl-lysine; SIRT1/2 dual inhibition; Sirtuin