Synthesis and calpain inhibitory activity of alpha-ketoamides with 2,3-methanoleucine stereoisomers at the P2 position.
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.
Donkor
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Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis 38163, USA. idonkor@utmem.edu
Zheng
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X
Miller
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D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors*; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry*; D013237:Stereoisomerism
C109266:2,3-methanoleucine; D000577:Amides; D002154:Calpain; D007930:Leucine