Publication Abstract from PubMed
We report a series of noncovalent, reversible inhibitors of cathepsin L that have been designed to explore additional binding interactions with the S' subsites. The design was based on our previously reported crystal structure that suggested the possibility of engineering increased interactions with the S' subsites ( Chowdhury et al. J. Med. Chem. 2002, 45, 5321-5329 ). A representative of these new inhibitors has been co-crystallized with mature cathepsin L, and the structure has been solved and refined at 2.2 A. The inhibitors described in this work extend farther into the S' subsites of cathepsins than any inhibitors reported in the literature thus far. These interactions appear to make use of a S3' subsite that can potentially be exploited for enhanced specificity and/or affinity.
Exploring inhibitor binding at the s' subsites of cathepsin L.,Chowdhury SF, Joseph L, Kumar S, Tulsidas SR, Bhat S, Ziomek E, Menard R, Sivaraman J, Purisima EO J Med Chem. 2008 Mar 13;51(5):1361-8. Epub 2008 Feb 16. PMID:18278855[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
