Sirtuin inhibitors as physiological research tools and therapeutic potentials have caught many attentions in last decades. The mimics of acyl lysine have been approved to be a very efficient strategy for development of mechanism-based sirtuin inhibitors. In current study, a novel scaffold of l-S-(3-carboxamidopropyl) cysteine (l-CAPC) has been exploited for design and synthesis of sirtuin inhibitors. As a result, the mimics of Nε-acyl-lysine derived from cysteine including small molecules (5a-m) and peptides (9a-m) have been synthesized. Among these, the peptides 9g and 9h were found to be the most inhibitory potency and selectivity against SIRT2.
Keywords: Mechanism-based inhibitors; SIRT2 inhibitors; Sirtuin inhibitors; The mimics of lysine; l-Cysteine.
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