Principles of mucin architecture: Structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains
Principles of mucin architecture: Structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains
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DOI：
10.1021/ja020208f
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发表时间：
2002-08-21
影响因子：
15
通讯作者：
Live, DH
中科院分区：
文献类型：
--
作者：
Coltart, DM;Royyuru, AK;Live, DH
用核磁共振技术研究了由细胞表面糖蛋白CD43的N-末端片段STTAV衍生的粘蛋白糖肽基序的结构特征。在这项研究中，通过全合成方法制备了一系列分子，包括多肽本身，三个在丝氨酸和苏氨酸侧链上分别与TN、Tf和STF糖类抗原具有α-O-糖基化聚集点的糖肽，以及一个与β-O连接的Tf抗原。此外，还研究了具有序列SSSAVAV的糖肽，该糖肽与Le(Y)表位进行了三糖基化。利用Tri-STF-STTAV糖肽的核磁共振数据，通过约束分子动力学计算来求解该结构。计算揭示了糖肽核心的一个确定的构象，它植根于多肽和第一个N-乙酰氨基半乳糖残基的相互作用。每个α-O连接的糖肽的核磁共振数据的相似性表明，这种结构在每个结构中都存在，第一糖和多肽的附着方式在建立核心的组织结构中是至关重要的。核心提供了一个公共框架，在该框架上可以显示各种多糖。值得注意的是，尽管α-多聚糖对多肽骨架有深刻的组织作用，但通过β-连接的结合几乎没有明显的结果。
The structural characteristics of a mucin glycopeptide motif derived from the N-terminal fragment STTAV of the cell surface glycoprotein CD43 have been investigated by NMR. In this study, a series of molecules prepared by total synthesis were examined, consisting of the peptide itself, three glycopeptides having clustered sites of alpha-O-glycosylation on the serine and threonine side chains with the Tn, TF, and STF carbohydrate antigens, respectively, and one with the beta-O-linked TF antigen. Additionally, a glycopeptide having the sequence SSSAVAV, triglycosylated with the Le(y) epitope, was investigated. NMR data for the tri-STF-STTAV glycopeptide were used to solve the structure of this construct through restrained molecular dynamics calculations. The calculations revealed a defined conformation for the glycopeptide core rooted in the interaction of the peptide and the first N-acetylgalactosamine residue. The similarity of the NMR data for each of the alpha-O-linked glycopeptides demonstrates that this structure persists for each construct and that the mode of attachment of the first sugar and the peptide is paramount in establishing the organization of the core. The core provides a common framework on which a variety of glycans may be displayed. Remarkably, while there is a profound organizational effect on the peptide backbone with the alpha-dinked glycans, attachment via a beta-linkage has little apparent consequence.