title: Interactions of low-molecular-weight semi-synthetic sulfated heparins with human leukocyte elastase and human Cathepsin G.
abstract: 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, K(i), and of the IC(50) 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. claudia.sissi@unipd.it
authors.forename: Claudia
authors.initials: C
authors.lastname: Sissi
authors.forename: Lorena
authors.initials: L
authors.lastname: Lucatello
authors.forename: Annamaria
authors.initials: A
authors.lastname: Naggi
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
authors.forename: Manlio
authors.initials: M
authors.lastname: Palumbo
mesh_terms: D000818:Animals; D001665:Binding Sites; D056649:Cathepsin G; D002403:Cathepsins / Q000737:chemistry*; D004347:Drug Interactions; D005944:Glucosamine / Q000737:chemistry; D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D006868:Hydrolysis; D007067:Iduronic Acid / Q000737:chemistry; D007700:Kinetics; D019272:Leukocyte Elastase / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009092:Mucous Membrane / Q000737:chemistry; D010447:Peptide Hydrolases / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry*; D013379:Substrate Specificity; D013552:Swine
chemical_list: D006495:Heparin, Low-Molecular-Weight; D007067:Iduronic Acid; D002403:Cathepsins; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D005944:Glucosamine