Peptidyl aldehyde inhibitors of calpain incorporating P2-proline mimetics.
Four new peptidyl aldehydes bearing proline mimetics at the P(2)-position were synthesized and studied as inhibitors of calpain I, cathepsin B, and selected serine proteases. The ring size of the P(2)-constraining residue influenced the inhibitory potency and selectivity of the compounds for calpain I compared to the other proteases.
Donkor
Isaac O
IO
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA. idonkor@utmem.edu
Korukonda
Rajani
R
Huang
Tien L
TL
LeCour
Louis
L
D000447:Aldehydes / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors*; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000201:enzymology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011392:Proline / Q000737:chemistry*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D011392:Proline; D002154:Calpain; D002401:Cathepsin B