1245943-01-4Relevant academic research and scientific papers
Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2
Huhtiniemi, Tero,Suuronen, Tiina,Lahtela-Kakkonen, Maija,Bruijn, Tanja,J??skel?inen, Sanna,Poso, Antti,Salminen, Antero,Lepp?nen, Jukka,Jarho, Elina
supporting information; experimental part, p. 5616 - 5625 (2010/09/14)
Sirtuins catalyze the NAD+ dependent deacetylation of N ε-acetyl lysine residues to nicotinamide, O′-acetyl-ADP- ribose (OAADPR) and Nε-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel Nε-modified lysine containing inhibitors against SIRT1 and SIRT2. Nε-Selenoacetyl and N ε-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied Nε-thioacetyl group. The Nε-3,3-dimethylacryl and Nε-isovaleryl moieties gave significant inhibition in comparison to the Nε-acetyl group present in the substrates. In addition, the studied Nε- alkanoyl, Nε-α,β-unsaturated carbonyl and N ε-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the Nε-modification. These results are applicable for further screening of Nε-acetyl analogues.
