Molecular docking of cathepsin L inhibitors in the binding site of papain.

ABSTRACT: The papain/CLIK-148 coordinate system was employed as a model to study the interactions of a nonpeptide thiocarbazate inhibitor of cathepsin L ( 1). This small molecule inhibitor, a thiol ester containing a diacyl hydrazine functionality and one stereogenic center, was most active as the S-enantiomer, with an IC 50 of 56 nM; the R-enantiomer ( 2) displayed only weak activity (33 microM). Correspondingly, molecular docking studies with Extra Precision Glide revealed a correlation between score and biological activity for the two thiocarbazate enantiomers when a structural water was preserved. The molecular interactions between 1 and papain were very similar to the interactions observed for CLIK-148 ( 3a and 3b) with papain, especially with regard to the hydrogen-bonding and lipophilic inter

SUBMITTER: Beavers MP 

PROVIDER: S-EPMC2923042 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature