Raman Karthik, Kuberan Balagurunathan, Arungundram Sailaja
Department of Bioengineering, University of Utah, Salt Lake City, UT, USA.
Methods Mol Biol. 2015;1229:31-6. doi: 10.1007/978-1-4939-1714-3_4.
Heparin is a potent clinically used anticoagulant. It is a heterogeneous mixture of polymers that contain a variety of sulfation patterns. However, only 3-O sulfonated heparin pentasaccharide units have been proven to bind to antithrombin and elicit an anticoagulant response. Heparins with other sulfation patterns are able to bind to a variety of other proteins such as FGF, VEGF, and CXCL-3. By modulating heparin's sulfation pattern, it is possible to generate polymers that can regulate biological processes beyond hemostasis. Here we describe a variety of simple chemical modification methods, N-acetylation, N-deacetylation, N-sulfation, O-sulfation, 2-O desulfation, and complete desulfation, to prepare heparin-like polymers with distinct sulfation patterns.
肝素是一种临床上常用的强效抗凝剂。它是聚合物的异质混合物，包含多种硫酸化模式。然而，只有3-O硫酸化的肝素五糖单元已被证明能与抗凝血酶结合并引发抗凝反应。具有其他硫酸化模式的肝素能够与多种其他蛋白质结合，如成纤维细胞生长因子（FGF）、血管内皮生长因子（VEGF）和CXC趋化因子配体3（CXCL-3）。通过调节肝素的硫酸化模式，可以生成能够调节止血以外生物过程的聚合物。在此，我们描述了多种简单的化学修饰方法，即N-乙酰化、N-脱乙酰化、N-硫酸化、O-硫酸化、2-O脱硫酸化和完全脱硫酸化，以制备具有不同硫酸化模式的类肝素聚合物。
