Please use this identifier to cite or link to this item: https://doi.org/10.1021/ja070870h
Title: Inhibitor fingerprinting of matrix metalloproteases using a combinatorial peptide hydroxamate library
Authors: Uttamchandani, M. 
Wang, J.
Li, J.
Hu, M.
Sun, H.
Chen, K.Y.-T. 
Liu, K.
Yao, S.Q. 
Issue Date: 27-Jun-2007
Source: Uttamchandani, M., Wang, J., Li, J., Hu, M., Sun, H., Chen, K.Y.-T., Liu, K., Yao, S.Q. (2007-06-27). Inhibitor fingerprinting of matrix metalloproteases using a combinatorial peptide hydroxamate library. Journal of the American Chemical Society 129 (25) : 7848-7858. ScholarBank@NUS Repository. https://doi.org/10.1021/ja070870h
Abstract: We report the inhibitor fingerprints of seven matrix metalloproteases, representing all five established families of this important class of enzymes, against a highly diversified small-molecule library. A total of 1400 peptide hydroxamates were individually prepared by systematically permuting both natural and unnatural amino acids across the P′1, P′ 2, and P′3 positions, thereby generating an inhibitor library with three-pronged structural diversity. High-throughput screenings were efficiently conducted in microtiter plate format, providing a rapid and quantitative determination of inhibitor potency across the panel of enzymes. Despite similarities in substrate preferences and structural homologies within this class of enzymes, our findings revealed distinct patterns of inhibition for each MMP against varied chemical scaffolds. The resulting inhibitor fingerprints readily facilitated the identification of inhibitors with good potency as well as desirable selectivity, potentially minimizing adverse effects when developing such leads into candidate drugs. The strategy also offers a novel method for the functional classification of matrix metalloproteases, on the basis of the characteristic profiles obtained using the diverse set of inhibitors. This approach thus paves the way forward in lead identification by providing a rapid and quantitative method for selectivity screening at the outset of the drug discovery process. © 2007 American Chemical Society.
Source Title: Journal of the American Chemical Society
URI: http://scholarbank.nus.edu.sg/handle/10635/94055
ISSN: 00027863
DOI: 10.1021/ja070870h
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

41
checked on Feb 15, 2018

WEB OF SCIENCETM
Citations

43
checked on Feb 7, 2018

Page view(s)

33
checked on Feb 20, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.