Liu Z, Perlin A S
Department of Chemistry, McGill University, Montreal, Que., Canada.
Carbohydr Res. 1992 Apr 10;228(1):29-36. doi: 10.1016/s0008-6215(00)90546-9.
A variety of chemical modifications can induce a reduction in the anticoagulant activity of heparin. Among such modifications are the removal in alkaline solution of the 2-O-sulfonate group of alpha-L-idopyranosyluronic acid 2-sulfate residues (1) and, in a weakly acidic medium, of the N-sulfonate group of residues of 2-deoxy-2-sulfamino-alpha-D-glucopyranose 6-sulfate (2). This study examined the possibility that the losses in anticoagulant potency are related to a concomitant removal of the 3-O-sulfonate group of residues of 2-deoxy-2-sulfamino-alpha-D-glucopyranose 3,6-disulfate (6) in the AT-III binding site. It entailed a synthesis of methyl 2-deoxy-2-sulfamino-alpha-D-glucopyranoside 3-sulfate (7), as a model compound that was subjected to both the strongly alkaline and weakly acidic conditions appropriate for the modification of residues 1 and 2, respectively. The 3-sulfate group of 7 was found to be highly stable in both environments. This indicated that the adverse effects that these conditions have on the anticoagulant properties of heparin are not specifically associated with the 3-sulfate substituent of residues of 6 in the polymer.
多种化学修饰可导致肝素抗凝活性降低。此类修饰包括在碱性溶液中去除硫酸化α-L-艾杜糖醛酸2-硫酸酯残基的2-O-磺酸基团（1），以及在弱酸性介质中去除2-脱氧-2-磺氨基-α-D-吡喃葡萄糖6-硫酸酯残基的N-磺酸基团（2）。本研究考察了抗凝效力降低是否与AT-III结合位点中2-脱氧-2-磺氨基-α-D-吡喃葡萄糖3,6-二硫酸酯（6）残基的3-O-磺酸基团同时去除有关。为此合成了2-脱氧-2-磺氨基-α-D-吡喃葡萄糖3-硫酸甲酯（7）作为模型化合物，分别使其经受适合修饰残基1和2的强碱性和弱酸性条件。结果发现7的3-硫酸基团在这两种环境中都高度稳定。这表明这些条件对肝素抗凝特性产生的不利影响并非与聚合物中6残基的3-硫酸取代基有特定关联。
