Tailored Design and Synthesis of Heparan Sulfate Oligosaccharide Analogues Using Sequential One-Pot Multienzyme Systems

摘要

Heparan sulfate (HS) and heparin are linear sulfated hetero polysaccharides that consist of alternating α1-4-linked D-glucosamines (GlcN) and 1-4-linked uronic acids, with an α-linkage for L-iduronic acid (IdoA) and a β-linkage for D-glucuronic acid (GlcA). Possible modifications include 2-O-sulfation on the uronic acid residues, and one or more modifications on the glucosamine residues, including N-sulfation, N-acetylation, 6-O-sulfation, and 3-O-sulfation. Heparin and low-molecular-weight heparin (LMWH) are the-most commonly used anticoagulants or antithrombotic drugs. Compared to HS, heparin has a higlher level of sulfation and a higher IdoA content. Heparin is mostly produced by mast cells, and heparan sulfates are produced by different cell types in animals. They are attractive synthetic targets because of the therapeutic application of heparin, and the important roles of HS and heparin in regulating cancer growth, blood coagulation, inflammation, assisting against viral and bacterial infections, signal transduction, lipid metabolism, and cell differentiation.