Kiviranta Päivi H, Suuronen Tiina, Wallén Erik A A, Leppänen Jukka, Tervonen Jussi, Kyrylenko Sergiy, Salminen Antero, Poso Antti, Jarho Elina M
Department of Pharmaceutical Chemistry, Institute of Clinical Medicine, University of Kuopio, Kuopio, Finland.
J Med Chem. 2009 Apr 9;52(7):2153-6. doi: 10.1021/jm801401k.
N()-Thioacetyl-lysine-containing tri-, tetra-, and pentapeptides, based on the alpha-tubulin and p53 protein sequences, were studied as SIRT1 and SIRT2 inhibitors. The potency of the pentapeptides depended on the selection of the side chains. The removal of N- and C-terminal residues of the pentapeptides yielded tripeptides with retained SIRT1 inhibitory activity but decreased SIRT2 inhibitory activity. The most potent SIRT1 inhibitors were equipotent with the reference compound (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) with the IC(50) values of 180-330 nM.
基于α-微管蛋白和p53蛋白序列，对含N()-硫代乙酰赖氨酸的三肽、四肽和五肽作为SIRT1和SIRT2抑制剂进行了研究。五肽的效力取决于侧链的选择。去除五肽的N端和C端残基后得到的三肽保留了SIRT1抑制活性，但SIRT2抑制活性降低。最有效的SIRT1抑制剂与参考化合物（6-氯-2,3,4,9-四氢-1H-咔唑-1-甲酰胺）效力相当，IC(50)值为180 - 330 nM。
