STRUCTURE-ACTIVITY RELATIONSHIP IN HEPARIN - A SYNTHETIC PENTASACCHARIDE WITH HIGH-AFFINITY FOR ANTI-THROMBIN-III AND ELICITING HIGH ANTI-FACTOR-XA ACTIVITY
STRUCTURE-ACTIVITY RELATIONSHIP IN HEPARIN - A SYNTHETIC PENTASACCHARIDE WITH HIGH-AFFINITY FOR ANTI-THROMBIN-III AND ELICITING HIGH ANTI-FACTOR-XA ACTIVITY
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DOI：
10.1016/0006-291x(83)90550-8
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发表时间：
1983-01-01
影响因子：
3.1
通讯作者：
GATTI, G
中科院分区：
文献类型：
--
作者：
CHOAY, J;PETITOU, M;GATTI, G
四糖的结构。- d -葡萄糖醛酸)4 (N-sulfate-3 6-di-O-sulfate -.alpha。.fwdarw -D-glucosamine) 1。4 (2-0-sulfate -.alpha。- l -碘醛酸)4（n -硫酸盐-6-0-硫酸盐- d -氨基葡萄糖）和五糖(n -硫酸盐-6-0-硫酸盐- α。.fwdarw -D-glucosamine) 1。4(度量。- d -葡萄糖醛酸)4 (N-sulfate-3 6-di-O-sulfate -.alpha。.fwdarw -D-glucosamine) 1。4 (2-0-sulfate -.alpha。- l -碘醛酸)4（n -硫酸盐-6-0-硫酸盐- d -氨基葡萄糖）均为首次由d -葡萄糖和d -氨基葡萄糖化学合成的化合物，经NMR确证。合成的四糖既不与人牛AT-III[抗凝血素- iii]结合，也不诱导该抑制剂的抗因子Xa活性增强。合成的五糖与AT-III （Ka: 7 .cntdot）强结合。106/M)形成等摩尔复合物，并增强AT-III对Xa因子的抑制活性。合成的具有上述结构的五糖明显符合肝素与AT-III结合所需的实际最小序列。[肝素主要通过与AT-III结合并增强该抑制剂的作用来抑制多种促凝蛋白酶]。
The structures of the tetrasaccharide (.beta.-D-glucuronic acid)1 .fwdarw. 4(N-sulfate-3,6-di-O-sulfate-.alpha.-D-glucosamine)1 .fwdarw. 4 (2-0-sulfate-.alpha.-L-iduronic acid)1 .fwdarw. 4(N-sulfate-6-0-sulfate-D-glucosamine) and of the pentasaccharide (N-sulfate-6-0-sulfate-.alpha.-D-glucosamine)1 .fwdarw. 4(.beta.-D-glucuronic acid)1 .fwdarw. 4(N-sulfate-3,6-di-O-sulfate-.alpha.-D-glucosamine)1 .fwdarw. 4(2-0-sulfate-.alpha.-L-iduronic acid)1 .fwdarw. 4(N-sulfate-6-0-sulfate-D-glucosamine), both prepared for the first time, by chemical synthesis from D-glucose and D-glucosamine, were confirmed by NMR. The synthetic tetrasaccharide neither binds to human bovine AT-III [antithrombin-III] nor induces anti-factor Xa activity enhancement of this inhibitor. The synthetic pentasaccharide strongly binds to AT-III (Ka: 7 .cntdot. 106/M) forming an equimolar complex and also enhances the AT-III inhibitory activity towards factor Xa. The synthetic pentasaccharide with the above structure evidently corresponds to the actual minimal sequence required in heparin for binding to AT-III. [Heparin inhibits a number of procoagulant proteases mainly by binding to AT-III and enhancing the effects of this inhibitor.].