A Hexasaccharide Containing Rare 2‐O‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II

• DOI: 10.1002/anie.201609541
• Publication Date: 2017-01-26T12:06:48Z
• Authors: Nehru Viji Sankar...; Tamara R. Strebel; Rio S. Boothello; Kevin Sheerin; Arjun Raghuraman; Florence Sallas; Philip D. Mosier; Nicholas D. Water...; Stefan Oscarson; Umesh R. Desai
• Keywords: Serpin; Heparin cofactor II; Chemical Biology

Abstract Glycosaminoglycan (GAG) sequences that selectively target heparin cofactor II (HCII), a key serpin present in human plasma, remain unknown. Using computational strategy on library of 46 656 heparan sulfate hexasaccharides we identified rare sequence consisting consecutive glucuronic acid 2‐ O ‐sulfate residues as targeting HCII. This and four other unique were chemically synthesized. The designed was found to activate HCII ca. 250‐fold, while leaving aside antithrombin, closely related serpin, essentially unactivated. group will help understand function. More importantly, our results show for the first time rigorous use techniques can lead discovery GAG GAG‐binding protein(s), which may chemical biology or drug tools.