Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L - Comparisons of potency and selectivity profiles with cathepsin B

Article abstract of DOI:10.1016/S0960-894X(00)00340-1

We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl α-keto-β-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a K(i)=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date. (C) 2000 Elsevier Science Ltd. All rights reserved.