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Thermodynamic profiles of the interactions of suramin, chondroitin sulfate, and pentosan polysulfate with the inhibitory domain of TIMP ‐3
Author(s) -
Logue Timothy,
LizotteWaniewski Michelle,
Brew Keith
Publication year - 2020
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 - 10.1002/1873-3468.13556
Subject(s) - isothermal titration calorimetry , chemistry , chondroitin sulfate , biophysics , extracellular matrix , extracellular , sulfation , endocytosis , biochemistry , glycosaminoglycan , receptor , biology
Extracellular levels of soluble TIMP ‐3 are low, reflecting its binding by extracellular matrix ( ECM ) components including sulfated glycosaminoglycans ( SGAG s) and endocytosis via low density lipoprotein receptor‐related protein 1. Since TIMP ‐3 inhibits ECM degradation, the ability of SGAG s to elevate extracellular TIMP ‐3 is significant for osteoarthritis treatment. Previous studies of such interactions have utilized immobilized TIMP ‐3 or ligands. Here, we report the thermodynamics of the interactions of the sGAG ‐binding N‐domain of TIMP ‐3 with chondroitin sulfate, pentosan polysulfate, and suramin in solution using isothermal titration calorimetry. All three interactions are driven by a favorable negative enthalpy change combined with an unfavorable decrease in entropy. The heat capacity changes (Δ C p ) for all of the interactions are zero, indicating an insignificant contribution from hydrophobic interactions.