Engineering of routes to heparin and related polysaccharides.
Engineering of routes to heparin and related polysaccharides.
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DOI：
10.1007/s00253-011-3641-4
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发表时间：
2012-01
影响因子：
5
通讯作者：
Linhardt, Robert J.
中科院分区：
文献类型：
--
作者：
Bhaskar, Ujjwal;Sterner, Eric;Hickey, Anne Marie;Onishi, Akihiro;Zhang, Fuming;Dordick, Jonathan S.;Linhardt, Robert J.
关键词：
抗凝肝素已被证明具有重要的生物学功能，这些功能因其精细结构而异。肝素结构的可变性是由于其生物合成和基于动物组织的恢复，并为其复杂的聚合物结构增加了另一个维度。链长和硫酸化模式的结构变化介导其与许多肝素结合蛋白的相互作用，从而引发复杂的生物反应。新的化学和酶合成多糖的方法的出现，加上药物发现的高通量组合方法，促进了对肝素结构-活性关系的理解。更好的理解将为通过多糖工程开发新的治疗方法提供潜力。这样的生物工程方法需要几个不同学科的融合，包括碳水化合物合成、应用酶学、代谢工程和过程生物化学。
Anticoagulant heparin has been shown to possess important biological functions that vary according to its fine structure. Variability within heparin's structure occurs owing to its biosynthesis and animal tissue-based recovery, and adds another dimension to its complex polymeric structure. The structural variations in chain length and sulfation patterns mediate its interaction with many heparin-binding proteins, thereby, eliciting complex biological responses. The advent of novel chemical and enzymatic approaches for polysaccharide synthesis coupled with high throughput combinatorial approaches for drug discovery have facilitated an increased effort to understand heparin's structure-activity relationships. An improved understanding would offer potential for new therapeutic development through the engineering of polysaccharides. Such a bioengineering approach requires the amalgamation of several different disciplines including carbohydrate synthesis, applied enzymology, metabolic engineering, and process biochemistry.
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