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

• Autorzy: Drabik P. , Politowska E. , Czaplewski C. , Kasprzykowski F. , Lankiewicz L. , Ciarkowski J.
• Języki publikacji: EN

Abstrakty

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.

Słowa kluczowe

EN

inhibitor development; covalent inhibitor; covalent protease inhibitor; papain; cysteine protease; molecular dynamics

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2000
• Tom: 47
• Numer: 4
• Opis fizyczny: p.1061-1066,fig.,ref.

Twórcy

autor

Drabik P.

• University of Gdansk, J.Sobieskiego 18, 80-952 Gdansk, Poland

autor

Politowska E.

autor

Czaplewski C.

autor

Kasprzykowski F.

autor

Lankiewicz L.

autor

Ciarkowski J.

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