Synthesis of sialic acid derivatives as ligands for the myelin-associated glycoprotein (MAG)
Synthesis of sialic acid derivatives as ligands for the myelin-associated glycoprotein (MAG)
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DOI：
10.1016/j.bmc.2007.04.038
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发表时间：
2007-07-15
影响因子：
3.5
通讯作者：
Ernst, Beat
中科院分区：
文献类型：
--
作者：
Shelke, Sachin V.;Gao, Gan-Pan;Ernst, Beat
神经节苷脂GQ 1b α的三糖亚结构13显示出对髓鞘相关糖蛋白（MAG）的显著亲和力。在寻找13的结构简化和药物动力学改进的模拟物时，合成了在还原和非还原末端具有修饰的唾液酸糖苷。模拟物12 a-o的生物学评价在基于竞争性靶标的测定中进行。结果发现，拮抗剂12 h的相对抑制效力（rIP）与参比三糖13相比提高了1000倍以上，尽管前者具有更简单的结构。此外，唾液酸衍生物，例如12 h，由于与参比化合物13相比存在芳族部分、较低的分子量和减少的极性羟基官能团的数量，具有明显改善的药代动力学性质。(c)2007爱思唯尔有限公司保留所有权利。
The trisaccharide substructure 13 of the ganglioside GQ1b alpha shows a remarkable affinity for the myelin-associated glycoprotein (MAG). In the search for structurally simplified and pharmacokinetically improved mimics of 13, sialosides with modifications at the reducing and non-reducing end were synthesized. The biological evaluation of mimics 12a-o was performed in a competitive target-based assay. It was found that the relative inhibitory potency (rIP) of antagonist 12h was enhanced by more than 1000-fold in comparison to the reference trisaccharide 13, despite the former having a much simpler structure. In addition, the sialic acid derivatives, for example, 12h, have clearly improved pharmacokinetic properties due to the presence of aromatic moieties, a lower molecular weight, and a reduced number of polar hydroxy functions compared to the reference compound 13. (c) 2007 Elsevier Ltd. All rights reserved.