Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L — comparisons of potency and selectivity profiles with cathepsin B
John F. Lynasa b✉, Susan J. Hawthornec d, Brian Walkerb c
- aDivision of Biomedicinal Chemistry, School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Northern Ireland, UK. j.lynas@qub.ac.uk
- bDivision of Biomedicinal Chemistry, School of Pharmacy, Queen s University Belfast, Medical Biology Centre, 79 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK
- cDivision of Biomedicinal Chemistry, School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 79 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK
- dSchool of Pharm. & Pharmaceut. Sc
- ✉Corresponding author
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Abstract
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 alpha-keto-beta-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki 0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date.
TL;DRKinetic evaluation of a new series of putative inhibitors of cathepsin L, based on di- and tri-peptidyl α-keto-β-aldehydes, revealed Z-Phe-Tyr(OBut)-COCHO, with a K i =0.6 nM, to be the most potent, synthetic reversible inhibitor ofCatheps in L reported to date. (Semantic Scholar)