Synthesis and calpain inhibitory activity of α-ketoamides with 2,3-methanoleucine stereoisomers at the P2 position

A series of novel ketoamides incorporating all four 2,3-methanoleucine stereoisomers at the P-2 position was synthesized. The compounds displayed a wide variation in K-i values for inhibition of calpain I depending on the configuration of the P-2 methanoleucine residue. However, similar variation in cathepsin B inhibition was not observed suggesting that the S-2 pocket of calpain I is more stereosensitive than that of cathepsin B. (C) 2000 Published by Elsevier Science Ltd.