title: Cyclic peptide-based potent human SIRT6 inhibitors.
abstract: We discovered in the current study that six side chain-to-side chain cyclic pentapeptides harboring a central N(ε)-dodecyl (or tetradecyl)-thiocarbamoyl-lysine residue all behaved as highly potent (nM level) inhibitors against human SIRT6-catalyzed deacylation reaction. Moreover, one compound was also found to be selective for SIRT6 versus SIRT2/3/5 (∼20-, ∼11-, and >940-fold, respectively), despite its modest (∼2.3-fold) SIRT6 inhibitory selectivity versus SIRT1. These compounds could be valuable leads for the identification of further potent and selective human SIRT6 inhibitors.
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, P. R. China. wzheng@ujs.edu.cn.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Liu
authors.forename: Weiping
authors.initials: W
authors.lastname: Zheng
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D000072417:Protein Domains; D037761:Sirtuins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C516592:SIRT6 protein, human; D037761:Sirtuins