C-terminal trans,trans-muconic acid ethyl ester partial retro-inverso pseudopeptides as proteasome inhibitors

摘要

The development of specific inhibitors of the proteasome represents an important opportunity for new drug therapies. The central role of the multicatalytic complex in the intracellular proteolysis mediated by ubiquitin-proteasome pathway goes to discovery many molecules able to selectively inhibits enzymatic active subsites. Now, we report synthesis and activity of a new partial retro-inverso oligopseudopeptide derivatives bearing a trans, transmuconic acid ethyl ester pharmacophoric unit at the C-terminal. Some analogues selectively inhibited in mu M range the caspase-like (C-L) activity in the beta 1 subunit of the proteasome.