title: Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases.
abstract: Sulfated low molecular weight lignins (LMWLs), designed as oligomeric mimetics of low molecular weight heparins (LMWHs), have been found to bind in exosite II of thrombin. To assess whether sulfated LMWLs recognize other heparin-binding proteins, we studied their effect on serine proteases of the coagulation, inflammatory and digestive systems. Using chromogenic substrate hydrolysis assay, sulfated LMWLs were found to potently inhibit coagulation factor XIa and human leukocyte elastase, moderately inhibit cathepsin G and not inhibit coagulation factors VIIa, IXa, and XIIa, plasma kallikrein, activated protein C, trypsin, and chymotrypsin. Competition studies show that UFH competes with sulfated LMWLs for binding to factors Xa and XIa. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold.
authors.affiliation: Department of Medicinal Chemistry, Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Henry
authors.forename: Jay N
authors.initials: JN
authors.lastname: Thakkar
authors.forename: Aiye
authors.initials: A
authors.lastname: Liang
authors.forename: Umesh R
authors.initials: UR
authors.lastname: Desai
mesh_terms: D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology; D001667:Binding, Competitive; D015195:Drug Design; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D008031:Lignin / Q000737:chemistry* / Q000494:pharmacology; D018716:Molecular Mimicry; D008970:Molecular Weight; D057057:Serine Proteases / Q000737:chemistry*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013431:Sulfates / Q000737:chemistry
chemical_list: D000925:Anticoagulants; D015842:Serine Proteinase Inhibitors; D013431:Sulfates; D006493:Heparin; D008031:Lignin; D057057:Serine Proteases