Heparin is a naturally occurring glycosaminoglycan isolated from animal tissues and is medically used as an anticoagulant drug. Adulteration attempts of isolated heparin with chondroitin sulfate in the past resulted in great safety concerns. Also, increasing demands on batch-to-batch homogeneity for better evaluation and control of its pharmacodynamic and pharmacokinetic properties kindled the development of synthetic routes for the production of heparin and its derivatives. The discovery of enzymes involved in glycosaminoglycan biosynthesis and their application in chemoenzymatic synthesis makes it feasible to generate low molecular weight heparins (LMWHs) and ultra-low molecular weight heparins (ULMWHs). Understanding the scope and limitations of these enzymes currently used in the production of synthetic heparins will help to achieve more defined heparins with controlled medicative properties. Here, we summarized the recent advances in the chemoenzymatic synthesis of LMW/ULMW heparins.

中文翻译：

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化学酶法合成超低和低分子量肝素。

肝素是一种从动物组织中分离出来的天然糖胺聚糖，在医学上被用作抗凝药物。过去，分离的肝素与硫酸软骨素的掺假尝试导致了极大的安全隐患。同样，为了更好地评估和控制其药代动力学和药代动力学特性，对批间均质性的要求不断提高，促使了肝素及其衍生物生产的合成途径的发展。糖胺聚糖生物合成中涉及的酶的发现及其在化学酶法合成中的应用使得生成低分子量肝素（LMWHs）和超低分子量肝素（ULMWHs）成为可能。了解目前在合成肝素生产中使用的这些酶的范围和局限性，将有助于获得具有可控药物特性的更明确的肝素。在这里，我们总结了LMW / ULMW肝素化学合成中的最新进展。