title: Synthesis and calpain inhibitory activity of alpha-ketoamides with 2,3-methanoleucine stereoisomers at the P2 position.
abstract: A series of novel ketoamides incorporating all four 2,3-methanoleucine stereoisomers at the P2 position was synthesized. The compounds displayed a wide variation in Ki values for inhibition of calpain I depending on the configuration of the P2 methanoleucine residue. However, similar variation in cathepsin B inhibition was not observed suggesting that the S2 pocket of calpain I is more stereosensitive than that of cathepsin B.
authors.affiliation: Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis 38163, USA. idonkor@utmem.edu
authors.forename: I O
authors.initials: IO
authors.lastname: Donkor
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: D D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors*; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C109266:2,3-methanoleucine; D000577:Amides; D002154:Calpain; D007930:Leucine