Structural basis for the potent calpain inhibitory activity of peptidyl alpha-ketoacids.
A series of peptidyl alpha-ketoacids and alpha-ketoesters was synthesized and studied as mu-calpain inhibitors. Docking studies revealed that the mu-calpain inhibitory activity of the compounds is influenced by hydrogen bonding interactions and the potential for ionic interaction with active site residues as well as placement of a planar N-terminal capping group into the S 3 pocket of the enzyme.
Donkor
Isaac O
IO
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. idonkor@utmem.edu
Assefa
Haregewein
H
Liu
Jiuyu
J
D000143:Acids / Q000737:chemistry* / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D000143:Acids; D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; D002154:Calpain