School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, 4072, Australia.
Macromol Biosci. 2020 Sep;20(9):e2000110. doi: 10.1002/mabi.202000110. Epub 2020 Jul 6.
The glycosaminoglycan heparin is a clinically important anticoagulant drug, primarily used to reduce the risk of blood clots (thrombosis) during surgery. Despite its importance in medicine and its continuous use over many decades, heparin suffers from several limitations associated with its heterogeneity and its extraction from animal tissues. In order to address these limitations, reversible addition-fragmentation chain transfer polymerization is utilized to prepare a library of heparin mimetic copolymers from the sulfonated monomers sodium 4-styrene sulfonate, potassium-3-sulfopropyl acrylate, potassium-3-sulfopropyl methacrylate, and sodium-2-acrylamido-2-methyl-1-propane sulfonate. Copolymers are prepared using combinations of two different monomers in various ratios. Monomer reactivity ratios are also determined for some representative monomer combinations, and all polymers are characterized by H NMR spectroscopy and gel permeation chromatography. The anticoagulant activities of the copolymers are determined by activated partial thromboplastin time and thrombin clotting time assays and structure-activity relationships are explored.
糖胺聚糖肝素是一种临床上重要的抗凝药物，主要用于降低手术过程中血液凝块（血栓）的风险。尽管肝素在医学上具有重要性，并且已经连续使用了几十年，但它仍然存在一些与其异质性及其从动物组织中提取有关的局限性。为了解决这些局限性，利用可逆加成-断裂链转移聚合反应，从磺化单体 4-苯乙烯磺酸钠、3-磺丙基丙烯酸钾、3-磺丙基甲基丙烯酸钾和 2-丙烯酰胺基-2-甲基-1-丙磺酸钠制备肝素模拟共聚体库。共聚体通过两种不同单体的不同组合来制备。还确定了一些代表性单体组合的单体反应性比，并且所有聚合物都通过 H NMR 光谱和凝胶渗透色谱法进行了表征。通过激活部分凝血活酶时间和凝血酶凝固时间测定来确定共聚物的抗凝活性，并探索了结构-活性关系。
