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我们能否以“大自然”为金标准来生产肝素/硫酸乙酰肝素仿生材料?

Can we produce heparin/heparan sulfate biomimetics using "mother-nature" as the gold standard?

作者信息

Farrugia Brooke L, Lord Megan S, Melrose James, Whitelock John M

机构信息

Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.

The Raymond Purves Research Labs, Institute of Bone and Joint Research, Kolling Institute of Medical Research, University of Sydney, The Royal North Shore Hospital of Sydney, St. Leonards, NSW 2065, Australia.

出版信息

Molecules. 2015 Mar 5;20(3):4254-76. doi: 10.3390/molecules20034254.

Abstract

Heparan sulfate (HS) and heparin are glycosaminoglycans (GAGs) that are heterogeneous in nature, not only due to differing disaccharide combinations, but also their sulfate modifications. HS is well known for its interactions with various growth factors and cytokines; and heparin for its clinical use as an anticoagulant. Due to their potential use in tissue regeneration; and the recent adverse events due to contamination of heparin; there is an increased surge to produce these GAGs on a commercial scale. The production of HS from natural sources is limited so strategies are being explored to be biomimetically produced via chemical; chemoenzymatic synthesis methods and through the recombinant expression of proteoglycans. This review details the most recent advances in the field of HS/heparin synthesis for the production of low molecular weight heparin (LMWH) and as a tool further our understanding of the interactions that occur between GAGs and growth factors and cytokines involved in tissue development and repair.

摘要

硫酸乙酰肝素(HS)和肝素是本质上具有异质性的糖胺聚糖(GAGs),这不仅是由于不同的二糖组合,还因其硫酸化修饰。HS因其与多种生长因子和细胞因子的相互作用而闻名;肝素则因其作为抗凝剂的临床应用而闻名。由于它们在组织再生中的潜在用途;以及近期因肝素污染导致的不良事件;以商业规模生产这些GAGs的需求激增。从天然来源生产HS受到限制,因此正在探索通过化学、化学酶促合成方法以及蛋白聚糖的重组表达进行仿生生产的策略。本综述详细介绍了HS/肝素合成领域的最新进展,用于生产低分子量肝素(LMWH),并作为一种工具,进一步加深我们对GAGs与参与组织发育和修复的生长因子及细胞因子之间相互作用的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb3c/6272578/6b0124a82f4a/molecules-20-04254-g001.jpg

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