Assembly of Novel Glycopeptides
One of My Postdoc Projects
Glycoproteins are important in many areas of biochemical processes including cell growth regulation, binding of pathogens to cells, intercellular communication and metastasis. Among other roles, the saccharide fragment in glycoproteins assists in protein folding and transmembrane transport, possibly by providing protection against proteolysis. The timing of N-linked glycosylation to an asparagine residue suggests that the carbohydrate may influence protein folding by altering the local secondary structure of the nascent polypeptide proximal to the glycosylatuion site. Read more: Unraveling the Mystery of Protein Folding by W. A. Thomasson
However, detailed information (for example by NMR) about the specific interactions of protein and the carbohydrate moieties are scarce, and limited to only a handful of accessible glycopeptides. We plan to study these interactions on a glycopeptide derived from a fully synthetic carbohydrate (and hence stereochemically defined) and a peptide. Very recently, we have achieved the first native chemical ligations to produce the world’s largest, fully synthetic, stereochemically defined materials for detailed NMR studies. The real thing, really clean! You will be reading about this one soon in the literature…
Publications
Z.-G. Wang, X. Zhang, M. Visser, D. Live, A. Zatorski, U. Iserloh, K. O. Lloyd and S. J. Danishefsky, Toward Fully Synthetic Homogeneous Glycoproteins: A High Mannose Core Containing Glycopeptide Carrying Full H-Type 2 Human Blood Group Specificity, Angew. Chem. Int. Ed 2001, 40, 1728-32. Download PDF.
D. Live, Z.-G. Wang, U. Iserloh, S. J. Danishefsky, A strategy for probing the autonomy of cross-domain stereochemical communication in glycoconjugates, Org. Lett 2001, 3, 851-54. Download PDF.