Principles of Mucin Architecture: Structural Studies on Synthetic Glycopeptides Bearing Clustered Mono-, Di-, Tri-, and Hexasaccharide Glycodomains
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- 作者：Don M. Coltart ; Ajay K. Royyuru ; Lawrence J. Williams ; Peter W. Glunz ; Dalibor Sames ; Scott D. Kuduk ; Jacob B. Schwarz ; Xiao-Tao Chen ; Samuel J. Danishefsky ; and David H. Live
- 刊名：Journal of the American Chemical Society
- 出版年：2002
- 出版时间：August 21, 2002
- 年：2002
- 卷：124
- 期：33
- 页码：9833 - 9844
- 全文大小：425K
- 年卷期：v.124,no.33(August 21, 2002)
- ISSN：1520-5126
文摘
The structural characteristics of a mucin glycopeptide motif derived from the N-terminal fragmentSTTAV of the cell surface glycoprotein CD43 have been investigated by NMR. In this study, a series ofmolecules prepared by total synthesis were examined, consisting of the peptide itself, three glycopeptideshaving clustered sites of 
-O-glycosylation on the serine and threonine side chains with the Tn, TF, andSTF carbohydrate antigens, respectively, and one with the 
-O-linked TF antigen. Additionally, a glycopeptidehaving the sequence SSSAVAV, triglycosylated with the Ley epitope, was investigated. NMR data for thetri-STF-STTAV glycopeptide were used to solve the structure of this construct through restrained moleculardynamics calculations. The calculations revealed a defined conformation for the glycopeptide core rootedin the interaction of the peptide and the first N-acetylgalactosamine residue. The similarity of the NMRdata for each of the -O-linked glycopeptides demonstrates that this structure persists for each constructand that the mode of attachment of the first sugar and the peptide is paramount in establishing theorganization of the core. The core provides a common framework on which a variety of glycans may bedisplayed. Remarkably, while there is a profound organizational effect on the peptide backbone with the-linked glycans, attachment via a -linkage has little apparent consequence.
-O-glycosylation on the serine and threonine side chains with the Tn, TF, andSTF carbohydrate antigens, respectively, and one with the -O-linked TF antigen. Additionally, a glycopeptidehaving the sequence SSSAVAV, triglycosylated with the Ley epitope, was investigated. NMR data for thetri-STF-STTAV glycopeptide were used to solve the structure of this construct through restrained moleculardynamics calculations. The calculations revealed a defined conformation for the glycopeptide core rootedin the interaction of the peptide and the first N-acetylgalactosamine residue. The similarity of the NMRdata for each of the -O-linked glycopeptides demonstrates that this structure persists for each constructand that the mode of attachment of the first sugar and the peptide is paramount in establishing theorganization of the core. The core provides a common framework on which a variety of glycans may bedisplayed. Remarkably, while there is a profound organizational effect on the peptide backbone with the-linked glycans, attachment via a -linkage has little apparent consequence.