Chemoenzymatic synthesis of classical and non-classical anticoagulant heparan sulfate polysaccharides
Chemoenzymatic synthesis of classical and non-classical anticoagulant heparan sulfate polysaccharides
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DOI：
10.1074/jbc.m305029200
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发表时间：
2003-12-26
影响因子：
4.8
通讯作者：
Rosenberg, RD
中科院分区：
文献类型：
--
作者：
Kuberan, B;Beeler, DL;Rosenberg, RD
硫酸乙酰肝素（HS）多糖与细胞表面的许多蛋白质相互作用，并协调许多不同的生物学功能。虽然HS的许多功能已经很好地建立，但只有少数特定的结构可以归因于HS功能。HS的极端多样性使得特定生物活性HS结构的化学合成成为一项繁琐和乏味的工作，需要费力和仔细的官能团操作。现在，许多参与HS生物合成的酶的特点，我们在这项研究中展示了如何可以快速，轻松地组装生物活性的HS结构与一组克隆的酶。我们已经证明了这种新方法的可行性，快速组装抗凝血酶III结合的经典和非经典的抗凝多糖结构的第一次。
Heparan sulfate (HS) polysaccharides interact with numerous proteins at the cell surface and orchestrate many different biological functions. Though many functions of HS are well established, only a few specific structures can be attributed to HS functions. The extreme diversity of HS makes chemical synthesis of specific bioactive HS structures a cumbersome and tedious undertaking that requires laborious and careful functional group manipulations. Now that many of the enzymes involved in HS biosynthesis are characterized, we show in this study how one can rapidly and easily assemble bioactive HS structures with a set of cloned enzymes. We have demonstrated the feasibility of this new approach to rapidly assemble antithrombin III-binding classical and non-classical anticoagulant polysaccharide structures for the first time.