Effect of structure modification of chondroitin sulfate C on its enantioselectivity to basic drugs in capillary electrophoresis.
Effect of structure modification of chondroitin sulfate C on its enantioselectivity to basic drugs in capillary electrophoresis.
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DOI：
10.1016/s0021-9673(01)01608-9
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发表时间：
2002-02
期刊：
影响因子：
--
通讯作者：
Yingxiang Du;A. Taga;Shigeo Suzuki;Wen-ying Liu;S. Honda
中科院分区：
文献类型：
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作者：
Yingxiang Du;A. Taga;Shigeo Suzuki;Wen-ying Liu;S. Honda
研究了硫酸软骨素C的结构修饰对其在毛细管电泳中对几种代表性碱性药物的对映选择性的影响。化学脱硫显示选择性没有显着下降，而用软骨素酶 ABC 解聚导致选择性完全丧失。与硫酸软骨素 A 比较表明，该异构体的选择性显着降低。脱硫衍生物中对映选择性的良好保留表明选择性来自于药物分子的一部分与硫酸软骨素C中除硫酸基团之外的官能团之间的多点机制中相互作用的大小的差异。硫酸基团不被认为对手性分离起主要作用。解聚导致的选择性完全丧失与较小糖类中选择性较低的一般趋势一致，硫酸软骨素 C 相对于硫酸软骨素 A 的优先性表明半乳糖胺残基中 C4 处羟基的重要性。在这项工作过程中，我们观察到一些批次的未涂层熔融石英毛细管在酸性条件下碱性药物峰存在大量拖尾，并通过用 Polybrene 和硫酸软骨素 C 双重涂层毛细管解决了这个问题。另一方面，我们证明了一种特殊技术的有用性，即使用短的、更宽口径的 PTFE 管连接毛细管来研究解聚的影响，以最大限度地减少样品量。
The effect of structure modification of chondroitin sulfate C on its enantioselectivity to several representative basic drugs in capillary electrophoresis was investigated. Chemical desulfation showed no remarkable decrease in selectivity, whereas depolymerization with chondroitinase ABC resulted in complete loss of selectivity. Comparison with chondroitin sulfate A indicated considerable decrease in selectivity with this isomer. The great retention of enantioselectivity in the desulfated derivative suggests that the selectivity comes from the difference of the magnitude of an interaction in the multipoint mechanism between a part of the drug molecule and a functional group in chondroitin sulfate C other than the sulfate group. The sulfate group is not considered to play a major role for chiral separation. The complete loss of selectivity by depolymerization is consistent with a general tendency of lower selectivity in smaller saccharides, and the priority of chondroitin sulfate C to chondroitin sulfate A suggests the importance of the hydroxyl group at C4in the galactosamine residue. During the course of this work we observed heavy tailing of the peaks of basic drugs in some batches of uncoated fused-silica capillaries under acidic conditions and solved this problem by doubly coating capillaries with Polybrene followed by chondroitin sulfate C. On the other hand, we demonstrated the usefulness of a special technique which uses a short, wider bore PTFE tube-attached capillary for the study of the effect of depolymerization, in order to minimize sample amount.