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Heparin‐like dextran derivatives as well as glycosaminoglycans inhibit the enzymatic activity of human cathepsin G
Author(s) -
Ledoux Dominique,
Merciris Didier,
Barritault Denis,
Caruelle Jean-Pierre
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00064-4
Subject(s) - chemistry , heparan sulfate , heparin , biochemistry , sulfation , cathepsin g , dermatan sulfate , glycosaminoglycan , plasmin , fibronectin , enzyme , dextran , elastase , extracellular matrix
Some synthetic dextran derivatives that mimic the action of heparin/heparan sulfate were previously shown to inhibit neutrophil elastase and plasmin. Here we report that these derivatized dextrans also inhibit cathepsin G (CatG). Dextran containing carboxymethyl and benzylamide groups (RG1150) as well as those containing carboxymethyl, sulfate and benzylamide groups (RG1192), were the most efficient inhibitors of CatG activity. RG1192 and RG1150 bind CatG with a K i of 0.11 and 0.17 nM, respectively, while carboxymethylated sulfated dextran (RG1503) as well as heparin, heparan sulfate and dermatan sulfate bind CatG with a 7‐ to 30‐fold lower affinity. Variation of K i with ionic strength indicates that ionic interactions account for 26% of the RG1503–CatG binding energy, while binding of RG1192 or RG1150 to CatG is mainly governed by non‐electrostatic interactions. This, together with the fact that these compounds both protect fibronectin and laminin against CatG‐mediated degradation, suggest that specific dextran derivatives can contribute to the regulation of CatG activity.