title: Novel sirtuin inhibitory warheads derived from the N(ε)-acetyl-lysine analog L-2-amino-7-carboxamidoheptanoic acid.
abstract: Built upon the catalytic mechanism-based pan-SIRT1/2/3 inhibitory warhead L-2-amino-7-carboxamidoheptanoic acid (L-ACAH, a close structural analog of N(ε)-acetyl-lysine) that our laboratory discovered recently, in the current study, its carboxamide NH2-ethylated analog was found to be a ∼2.4-6.6-fold stronger SIRT1/2/3 inhibitory warhead than L-ACAH. Carboxamide NH2-dodecylated and carboxymethylated analogs of L-ACAH were also identified as potent SIRT6 and SIRT5 inhibitory warheads, respectively.
authors.affiliation: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, P. R. China. wzheng@ujs.edu.cn.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: He
authors.forename: Lingling
authors.initials: L
authors.lastname: Yan
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zang
authors.forename: Weiping
authors.initials: W
authors.lastname: Zheng
mesh_terms: D006538:Heptanoic Acids / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008239:Lysine / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D006538:Heptanoic Acids; C000609652:L-2-amino-7-carboxamidoheptanoic acid; D054852:Small Molecule Libraries; D037761:Sirtuins; D008239:Lysine