Synthesis of heparin-like oligosaccharides on polymer supports
Synthesis of heparin-like oligosaccharides on polymer supports
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DOI：
10.1023/b:glyc.0000045091.18392.a8
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发表时间：
2004-01-01
影响因子：
3
通讯作者：
Martín-Lomas, M
中科院分区：
文献类型：
--
作者：
Ojeda, R;Terentí, O;Martín-Lomas, M
硫酸乙酰肝素糖胺聚糖调节多种蛋白质的生物学功能。为了便于阐明糖胺聚糖-蛋白质相互作用的分子基础，我们开发了在聚合物载体上合成肝素样寡糖的方法。一个完全立体选择性的战略，我们以前开发的这些寡糖在溶液中的合成已扩展到固相使用受体结合的方法。已经使用可溶性聚合物支持物和聚乙二醇接枝的聚苯乙烯树脂，并且已经探索了用于将受体连接到支持物的不同策略。通过糖醛酸单元的羧基通过琥珀酸酯键将完全受保护的二糖结构单元连接到可溶性支持物上，使用三氯乙酰亚胺酯作为糖基化剂和使用官能化的Merryfield型树脂用于加帽过程，允许构建含有肝素常规区域的结构基序的六糖和八糖片段。这种策略可以通过使用糖基化序列中所需的结构单元来促进糖胺聚糖低聚糖的合成。
The biological functions of a variety of proteins are regulated by heparan sulfate glycosaminoglycans. In order to facilitate the elucidation of the molecular basis of glycosaminoglycan-protein interactions we have developed syntheses of heparin-like oligosaccharides on polymer supports. A completely stereoselective strategy previously developed by us for the synthesis of these oligosaccharides in solution has been extended to the solid phase using an acceptor-bound approach. Both a soluble polymer support and a polyethylene glycol-grafted polystyrene resin have been used and different strategies for the attachment of the acceptor to the support have been explored. The attachment of fully protected disaccharide building blocks to a soluble support through the carboxylic group of the uronic acid unit by a succinic ester linkage, the use of trichloroacetimidates as glycosylating agents and of a functionalized Merryfield type resin for the capping process allowed for the construction of hexasaccharide and octasaccharide fragments containing the structural motif of the regular region of heparin. This strategy may facilitate the synthesis of glycosaminoglycan oligosaccharides by using the required building blocks in the glycosylation sequence.