title: Simple N(ε)-thioacetyl-lysine-containing cyclic peptides exhibiting highly potent sirtuin inhibition.
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.
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, PR China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yan
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: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; C513649:N(epsilon)-thioacetyllysine; D010456:Peptides, Cyclic; D037761:Sirtuins; D008239:Lysine
keywords: Catalytic mechanism-based; Cyclic peptide; Inhibitor; Sirtuin