Bivalent SIRT1 inhibitors.
In the current study, bivalent compounds 1-17 constructed by covalently linking the ɛ-amino group of lysine in a tripeptidic scaffold to a functionality via a linker were prepared and examined for their inhibitory potencies against SIRT1, a prototypical member of the β-nicotinamide adenine dinucleotide (β-NAD+)-dependent sirtuin family of protein Nε-acyl-lysine deacylases. A few of them were found to be stronger SIRT1 inhibitors than the Nɛ-acetyl-lysine-containing monovalent counterparts 18 and 19. As exemplified with compounds 6 and 18, a bivalent SIRT1 inhibitor could exhibit a greater degree of inhibitory selectivity among SIRT1/2/3 than the corresponding monovalent counterpart. This study has laid a foundation for the future development of superior bivalent inhibitors against the (patho)physiologically and therapeutically important sirtuin family of deacylase enzymes.
['Wang|Juan|J|', 'Zang|Wenwen|W|', 'Liu|Jiajia|J|', 'Zheng|Weiping|W|']
D056572:Histone Deacetylase Inhibitors D006801:Humans D007700:Kinetics D009842:Oligopeptides D056564:Sirtuin 1 D056565:Sirtuin 2 D056566:Sirtuin 3
Bivalent SIRT1 Inhibitor Sirtuin