Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases

► Sulfated LMWLs potently inhibit factor XIa, leukocyte elastase and cathepsin G. ► Sulfated LMWLs do not inhibit factors VIIa, IXa, and XIIa, activated protein C and plasma kallikrein. ► Sulfated LMWLs compete with heparin for binding to factors Xa and XIa. ► The results will aid the design of anticoagulants based on the sulfated LMWL scaffold. 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 [12]. 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.