Subsite requirements for peptide aldehyde inhibitors of human calpain I

Synthesis and structural studies of new N‐(p‐toluenesulfonyl)amino acid o‐phenolamides

“…Chemical shifts (ppm) are relative to (CH 3 ) 4 Si for 1 H and 13 C NMR and CH 3 NO 2 for 15 N NMR. Infrared spectra were recorded on a PerkinElmer System 200 FT-IR spectrophotometer.…”

QSAR studies on peptide α-ketoamides and α-ketohydroxamate derivatives as calpain I inhibitors

“…These inhibitors permanently inactivate calpain by displacing the active site cysteine thiol to form a sulfide. Reversible inhibitors include peptidyl aldehydes [13,14] and activated ketones [15,16] like a-ketoesters, a-keto-acids, and a-keto-amides. These inhibitors inactivate calpain in a transient manner by forming a reversible covalent bond (hemithioacetal or hemithioketal) with the cysteine thiol [17].…”

Synthesis of Novel Sulfonamide-Based Calpain Inhibitors and Their Potential as Anti-Tumor Agents

“…13 The incorporation of aliphatic (Val, Nle, Leu, Abu, Cha, and Met) and aromatic (Phe, Tyr(O-Benzyl)) at the P 1 position resulted in compounds with good or moderate calpain I inhibitory activity. 157 Hydrophobic groups will enhance potency while incorporation of amino acids which are capable of hydrogen bonding does not increase potency (such as Ser, Thr, Gln and Tyr) 157 and is detrimental to binding. 13 Aromatic amino acids are less potent than aliphatic amino acids.…”

“…13 Aromatic amino acids are less potent than aliphatic amino acids. 157 No substituted group, Gly, is detrimental to activity, compared with Ala. …”

“…157 Besides acidic or basic amino acids are not beneficial at P 2 . 157 A recent study showed that peptides with D-amino acids at P 2 postion were also potent calpain inhibitors. 158 …”