Design Synthesis and Evaluation of Heparan Sulfate Mimicking Glycopolymers for Inhibiting Heparanase Activity

摘要

Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics. This glycopolymer also lacks anticoagulant activity.