Principles of mucin architecture: Structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains Journal Article
| Authors: | Coltart, D. M.; Royyuru, A. K.; Williams, L. J.; Glunz, P. W.; Sames, D.; Kuduk, S. D.; Schwarz, J. B.; Chen, X. T.; Danishefsky, S. J.; Live, D. H. |
| Article Title: | Principles of mucin architecture: Structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains |
| Abstract: | 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 α-O-glycosylation on the serine and threonine side chains with the Tn, TF, and STF carbohydrate antigens, respectively, and one with the β-O-linked TF antigen. Additionally, a glycopeptide having the sequence SSSAVAV, triglycosylated with the Ley 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 α-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 α-linked glycans, attachment via a β-linkage has little apparent consequence. |
| Keywords: | unclassified drug; protein conformation; proteins; molecular dynamics; protein binding; amino acid sequence; molecular sequence data; antigens; protein synthesis; glycosylation; nuclear magnetic resonance spectroscopy; models, molecular; polysaccharide; antigens, cd; protein structure; structure analysis; polysaccharides; glycoprotein; nuclear magnetic resonance; carbohydrate sequence; carbohydrates; carbohydrate antigen; glycan derivative; glycopeptide; glycopeptides; protein modification; calculation; mucin; sugar; mucins; nuclear magnetic resonance, biomolecular; hexasaccharide; circular dichroism; chemical engineering; article; sialoglycoproteins; clustered sites; antigens, cd43 |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 124 |
| Issue: | 33 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2002-08-21 |
| Start Page: | 9833 |
| End Page: | 9844 |
| Language: | English |
| DOI: | 10.1021/ja020208f |
| PUBMED: | 12175243 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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