Novel sirtuin inhibitory warheads derived from the N-epsilon-acetyl-lysine analog L-2-amino-7-carboxamidoheptanoic acid

作者：He, Yanhua; Yan, Lingling; Zang, Wenwen; Zheng, Weiping^*

来源：Organic and Biomolecular Chemistry, 2015, 13(42): 10442-10450.

DOI：10.1039/c5ob01721a

• THIOACETYL-LYSINE
• METABOLISM
• DISCOVERY
• POTENT
• SIR2

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-epsilon-acetyl-lysine) that our laboratory discovered recently, in the current study, its carboxamide NH2-ethylated analog was found to be a similar to 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.

• 出版日期2015
• 单位江苏大学