Peptidyl β-homo-aspartals: Specific inhibitors of interleukin-1β converting enzyme and its homologues (caspases)

• Published in: Bioorganic & medicinal chemistry letters 1998-06, Vol.8 (12), p.1477-1482
• Main Authors: Bajusz, Sándor, Fauszt, Irén, Németh, Klára, Barabás, Éva, Juhász, Attila, Patthy, Miklós
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Aspartic Acid - analogs & derivatives; Aspartic Acid - pharmacology; Biological and medical sciences; Caspase 1 - metabolism; Caspase Inhibitors; Cysteine Proteinase Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Hydrolases; Substrate Specificity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00244-3

Inhibition of interleukin-1β converting enzyme (ICE), apopain, papain, thrombin and trypsin with substrate like peptidyl L- and D-α-aldehydes and their L-β-homo-aldehyde analogues was investigated. The L-β-homo-aspartals appear to be specific inhibitors for ICE and its homologues; the other enzymes were not inhibited with such L-β-homo aldehydes. Papain shows tolerance for D-residues at P 1 depending on their chiral stability. Substrate like peptidyl L-β-homo-aspartals inhibit interleukin-1β converting enzyme (ICE) and homologues, e.g. apopain; other enzymes, e.g. papain, thrombin and trypsin, were not inhibited with such L-β-homo aldehydes. Papain shows tolerance for D-residues at P; depending on their chiral stability.