Bending Trisaccharides by a Chelation-Induced Ring Flip of a Hinge-Like Monosaccharide Unit
Bending Trisaccharides by a Chelation-Induced Ring Flip of a Hinge-Like Monosaccharide Unit
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通过铰链状单糖单元的螯合诱导环翻转来弯曲三糖
DOI：
10.1021/ja984062p
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发表时间：
1999
影响因子：
15
通讯作者：
H. Hashimoto
中科院分区：
文献类型：
--
作者：
H. Yuasa;H. Hashimoto
螯合诱导的多肽构象变化是从头蛋白质设计中的一种有用策略，1其最终目的是构建具有定制结构和功能的人工蛋白质。采用这种策略与低聚糖可能会导致新的糖基架构的发展。虽然在某些天然多糖的溶液中加入金属离子会导致卷曲-螺旋转变2，3，并且某些单糖会因加入金属离子而发生环构象平衡的变化，2，4但金属离子对这些构象性质的影响程度通常很小，并且不会产生异常的构象。在这项研究中，我们通过2，4-二氨基-2，4-二脱氧-β-D-吡喃木糖苷单元的铰链样4C 1-至-1C4环翻转，创建了三聚体2和3的新型转角结构（图1）。这种环翻转是由柔性环结构5和1，3-双轴取向的二氨基的强螯合能力实现的。6通过1H NMR研究了甲基糖苷1和铰链单元在加入金属离子时的构象行为。甲基糖苷1是由已知化合物47经五步合成的（方案1）。采用2，4-二叠氮基-2，4-二脱氧吡喃葡萄糖苷衍生物8和R-吡喃木糖糖苷衍生物9的合成方法合成了关键中间体7。7的Birch还原得到化合物1。设计三糖链2和3以模拟复合N-连接聚糖的三糖序列（Galβ1-3GlcNAcβ1- 2 ManR）10，其中中心糖GlcNAc被铰链单元取代。通过将7转化为1-O-三氯乙酰亚胺酯10，然后通过施密特法11转化10，得到二糖11和12，从而在1的还原端引入甘露糖单元。半乳糖残基通过三氯乙酰基掺入到11和12中。
Chelation-induced conformational change of polypeptides is a useful strategy in de novo protein design, 1 which ultimately aims at the construction of artificial proteins with tailor-made structures and functionalities. Employing this strategy with oligosaccharides may lead to the development of novel sugar-based architectures. Although the addition of metal ions to solutions of some natural polysaccharides causes coil-helix transitions2, 3 and some monosaccharides undergo shifts in the ring conformation equilibrium by the addition of metal ions, 2, 4 the extent to which metal ions influence these conformational properties is usually small, and no extraordinary conformations are created. In this study, we created a novel turn structure of the trisaccharides 2 and 3 by a hinge-like 4C1-to-1C4 ring flip of the 2, 4-diamino-2, 4-dideoxy-β-D-xylopyranoside unit (Figure 1). This ring flip was enabled by the flexible ring structure5 and the strong chelating ability of diamino groups in the 1, 3-diaxial orientation. 6 Conformational behavior of the methyl glycoside 1 and that of the hinge unit on addition of metal ions were investigated by 1H NMR.The methyl glycoside 1 was synthesized in five steps from the known compound 47 (Scheme 1). The methods for synthesizing 2, 4-diazido-2, 4-dideoxy derivatives of glucopyranoside8 and R-xylopyranoside9 were employed for the synthesis of the key intermediate 7. Birch reduction of 7 gave the compound 1. The trisaccharides 2 and 3 were designed to mimic the trisaccharide sequence (Galβ1-3GlcNAcβ1-2ManR) 10 of complex N-linked glycans, in which the central sugar, GlcNAc, is replaced with the hinge unit. Introduction of the mannose units at the reducing end of 1 was accomplished by conversion of 7 into the 1-O-trichloroacetimidate 10 and then conversion of 10 by the Schmidt method11 to give disaccharides 11 and 12. Galactose residues were incorporated into 11 and 12 by the trichloroace-