Sugar-assisted glycopeptide ligation with complex oligosaccharides: scope and limitations.
Sugar-assisted glycopeptide ligation with complex oligosaccharides: scope and limitations.
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DOI：
10.1021/ja8010513
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发表时间：
2008-09-10
影响因子：
15
通讯作者：
Wong, Chi-Huey
中科院分区：
文献类型：
--
作者：
Bennett, Clay S.;Dean, Stephen M.;Payne, Richard J.;Ficht, Simon;Brik, Ashraf;Wong, Chi-Huey
我们以前已经证明，糖辅助结扎(SAL)是一种有效的糖肽聚合构建方法。然而，到目前为止，SAL仅在硫醇辅助物连接到单糖的系统中进行。为了使SAL真正适用于构建完全精细的糖肽和糖蛋白，必须能够在硫醇辅助物连接到更精细的糖上时进行反应，因为这些通常是在自然界中观察到的。在这里，我们研究了含C-2辅助糖链的C-3、C-4和C-6位糖基化的影响。模拟糖肽，用化学酶法合成，并与我们以前工作中使用的多肽硫酯反应。这些研究表明，SAL对辅助糖链上的糖基化反应非常敏感。虽然可以在C-4和C-6上延长糖基化来进行SAL，但C-3上糖基化的存在阻止了连接的发生。此外，在C-4糖基化的情况下，连接效率受到N-末端氨基酸的同一性的影响，而多肽硫酯的C-末端残基的性质似乎不会影响连接效率。这些研究为决定何时将SAL用于合成复杂的糖肽和糖蛋白以及如何设计连接连接以获得最佳产率提供了有用的指导。
We have previously shown sugar-assisted ligation (SAL) to be a useful method for the convergent construction of glycopeptides. However to date SAL has only been carried out on systems where the thiol auxiliary is attached to a monosaccharide. For SAL to be truly applicable to the construction of fully elaborated glycopeptides and glycoproteins it must be possible to carry out the reaction when the thiol auxiliary is attached to more elaborate sugars, as these are frequently what are observed in nature. Here we examine the effects of glycosylation at C-3, C-4 and C-6 of the C-2 auxiliary-containing glycan. Model glycopeptides where synthesized chemoenzymatically and reacted with peptide thioesters used in our previous work. These studies reveal that SAL is sensitive to extended glycosylation on the auxiliary-containing sugar. While it is possible to carry out SAL with extended glycosylation at C-4 and C-6, the presence of glycosylation at C-3 prevents the ligation from occurring. Additionally, with glycosylation at C-4 the ligation efficiency is affected by the identity of the N-terminal AA, while the nature of the C-terminal residue of the peptide thioester does not appear affect ligation efficiency. These studies provide useful guidelines in deciding when it is appropriate to use SAL in the synthesis of complex glycopeptides and glycoproteins, and how to design ligation junctions for optimal yield.
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影响因子：
3.1
作者：
Akaike, E;Tsutsumida, M;Fujita, K
通讯作者：
Fujita, K
影响因子：
56.9
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
通讯作者：
KENT, SBH
影响因子：
15
作者：
Brik, A;Yang, YY;Wong, CH
通讯作者：
Wong, CH
影响因子：
15
作者：
Hackenberger, CPR;Friel, CT;Imperiali, B
通讯作者：
Imperiali, B
影响因子：
4.3
作者：
Brik, Ashraf;Wong, Chi-Huey
通讯作者：
Wong, Chi-Huey