Interactions of low-molecular-weight semi-synthetic sulfated heparins with human leukocyte elastase and human Cathepsin G

Add time:08/20/2019    Source:sciencedirect.com

Semi-synthetic low-molecular-weight heparin samples (LMWHs), having homogeneous degree of polymerization and saccharide backbone, but differing in the number and location of sulfate groups, were investigated in their ability to interfere with the pharmacologically relevant targets human leukocyte elastase (EL) and human Cathepsin G (CatG). Spectroscopic studies were performed for a quantitative evaluation of the enzyme-inhibitor dissociation constant, Ki, and of the IC50 values for the inhibition of cleavage of target peptide sequences. Both proteases are inhibited by the tested polysaccharides through a mixed hyperbolic binding process. A non-linear relationship was found between degree of sulfation and binding affinity or enzyme inhibition properties, showing a composite correlation between heparin charge density and interference with EL/CatG activity.

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