N(epsilon)-thioacetyl-lysine-containing tri-, tetra-, and pentapeptides as SIRT1 and SIRT2 inhibitors.
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.
Kiviranta
Päivi H
PH
Department of Pharmaceutical Chemistry, Institute of Clinical Medicine, University of Kuopio, Kuopio, Finland.
Suuronen
Tiina
T
Wallén
Erik A A
EA
Leppänen
Jukka
J
Tervonen
Jussi
J
Kyrylenko
Sergiy
S
Salminen
Antero
A
Poso
Antti
A
Jarho
Elina M
EM
D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
C513649:N(epsilon)-thioacetyllysine; D009842:Oligopeptides; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D008239:Lysine