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2000 | 47 | 4 | 1061-1066
Article title

Theoretical studies of binding modes of two covalent inhibitors of cysteine proteases.

Content
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EN
Abstracts
EN
Physiological and pathological roles of cysteine proteases make them important targets for inhibitor development. Although highly potent inhibitors of this group of enzymes are known, their major drawback is a lack of sufficient specificity. Two cysteine protease covalent inhibitors, viz. (i) Z-RL-deoxo-V-peptide-epoxysuccinyl hybrid, and (ii) Z-RLVG-methyl-, have been developed and modeled in the catalytic pocket of papain, an archetypal thiol protease. A number of configurations have been generated and relaxed for each system using the AMBER force field. The catalytic pockets S3 and S4 appear rather elusive in view of the observed inhibitors' flexibility. This suggest rather limited chances for the development of selective structure-based inhibitors of thiol proteases, designed to exploit differences in the structure of catalytic pockets of various members of this family.
Publisher

Year
Volume
47
Issue
4
Pages
1061-1066
Physical description
Dates
published
2000
received
2000-03-13
revised
2000-07-24
accepted
2000-11-9
Contributors
author
  • Department of Public Health, University School of Physical Education, Gdańsk, Poland
  • Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland
  • Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland
  • Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland
  • Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland
  • Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland
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Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv47i4p1061kz
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