Simple Nε-thioacetyl-lysine-containing cyclic peptides exhibiting highly potent sirtuin inhibition

Transforming a linear pentapeptidic pan-SIRT1/2/3 inhibitor harboring the catalytic mechanism-based sirtuin inhibitory warhead Nε-thioacetyl-lysine into its side chain-to-side chain cyclized derivatives was able to furnish highly potent SIRT1/2/3 inhibition (low nM). This finding attests to the feasibility of developing structurally simple yet highly potent catalytic mechanism-based cyclic peptidic sirtuin inhibitors.

Highly potent SIRT1/2/3 inhibition was realized by transforming a linear peptidic pan-SIRT1/2/3 inhibitor harboring the catalytic mechanism-based sirtuin inhibitory warhead Nε-thioacetyl-lysine into its cyclized derivatives.Figure optionsDownload as PowerPoint slide