Vaidyanathan Deepika, Williams Asher, Dordick Jonathan S, Koffas Mattheos A G, Linhardt Robert J
Dept. of Biology Rensselaer Polytechnic Institute Troy NY 12180.
Dept. of Chemical and Biological Engineering Rensselaer Polytechnic Institute Troy NY 12180.
Bioeng Transl Med. 2017 Mar;2(1):17-30. doi: 10.1002/btm2.10042. Epub 2016 Nov 21.
Heparin is an anionic polysaccharide that is widely used as a clinical anticoagulant. This glycosaminoglycan is prepared from animal tissues in metric ton quantities. Animal-sourced heparin is also widely used in the preparation of low molecular weight heparins that are gaining in popularity as a result of their improved pharmacological properties. The recent contamination of pharmaceutical heparin together with concerns about increasing demand for this life saving drug and the fragility of the heparin supply chain has led the scientific community to consider other potential sources for heparin. This review examines progress toward the preparation of engineered heparins through chemical synthesis, chemoenzymatic synthesis, and metabolic engineering.
肝素是一种阴离子多糖,广泛用作临床抗凝剂。这种糖胺聚糖是以公吨数量从动物组织中制备的。动物源肝素也广泛用于制备低分子量肝素,由于其改善的药理学特性,低分子量肝素越来越受欢迎。近期药用肝素受到污染,加上对这种救命药物需求不断增加以及肝素供应链脆弱性的担忧,促使科学界考虑肝素的其他潜在来源。本综述考察了通过化学合成、化学酶促合成和代谢工程制备工程化肝素方面的进展。