Chemical synthesis of CD52 glycopeptides containing the acid-labile fucosyl linkage
Chemical synthesis of CD52 glycopeptides containing the acid-labile fucosyl linkage
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DOI：
10.1021/jo034773s
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发表时间：
2003-11-14
影响因子：
3.6
通讯作者：
Guo, ZW
中科院分区：
文献类型：
--
作者：
Shao, N;Xue, J;Guo, ZW
通过两种方法制备了糖肽 1，其中岩藻糖基化三糖 β-D-GlcNAc(1-->4)[α-L-Fuc(1-->6)]-β-D-GlcNAc 连接到 CD52 肽的 Asn，这两种方法都使用游离糖基 Asn 12 和糖三肽 21 作为关键中间体。因此，在制备三糖并连接至Asn后，将碳水化合物部分脱保护以得到12。通过仅在N末端延长肽链，在均质NMP溶液中从12构建21。虽然糖肽很容易溶于NMP，但由于存在游离三糖，它们几乎不溶于乙醚。因此，向反应混合物中添加乙醚可以沉淀糖肽，并且产物可以方便地以固体形式分离和纯化。 21 与游离九肽 24 在 NMP 中偶联得到 1。还使用酸敏感的 2-氯三苯甲基树脂通过固相合成制备了 1。在这种情况下，21 连接到树脂上的九肽上，然后用稀乙酸释放所得糖肽。在中等酸性条件下，肽的脱保护得到1。酸不稳定的α-岩藻糖在这些合成中不受影响。
Glycopeptide 1 with the fucosylated trisaccharide, beta-D-GlcNAc(1-->4)[alpha-L-Fuc(1-->6)]-beta-D-GlcNAc, linked to the Asn of CD52 peptide was prepared by two methods, both of which used the free glycosyl Asn 12 and glycotripeptide 21 as key intermediates. Thus, after the trisaccharide was prepared and linked to Asn, the carbohydrate moiety was deprotected to give 12. From 12, 21 was constructed in homogeneous NMP solutions by elongating the peptide chain alone the N-terminus. Though the glycopeptides were easily soluble in NMP, they were barely soluble in diethyl ether, because of the free trisaccharide. Consequently, addition of diethyl ether to the reaction mixtures could precipitate the glycopeptides, and the products were conveniently isolated and purified in the solid form. The coupling of 21 with a free nonapeptide 24 in NMP afforded 1. 1 was also prepared by solid-phase synthesis, using the acid-sensitive 2-chlorotrityl resin. In this case, 21 was attached to the nonapeptide on the resin, and the resulting glycopeptide was then released with dilute acetic acid. Deprotection of the peptide under moderate acidic conditions gave 1. The acid-labile alpha-fucose was not affected in these syntheses.