CUR - The Council on Undergraduate Research

The Synthesis and Modeling of Carbon-linked Glycopeptides with Observed Incorporation into a Salivary Protein (Mucin 7) Polypeptide Subunit as Glycosylation-based Antigens

Tanner Hahn, and Dr. Kristopher Waynant, Department of Chemistry, University of Idaho, 875 Perimeter Dr, Moscow, ID 83844

Glycomics, the complex organization of carbohydrate macromolecules on cells are found in many organisms throughout the natural world. The process of glycosylation directly impacts the biochemical function of intracellular proteins. Mucin7, a human saliva protein, is thought to act as an oral lubricant but there is some evidence that it may play an antibiotic role in the oral environment. After screening this protein, a small 23-peptide tandem repeat with high threonine and serine concentration for O-glycosylation has been selected. To evaluate this peptide unit as a potential immunostimulant or agglutination agent we are synthesizing carbon linked serine congeners to lock the starting sugars in place. As observed with other sphingolipids and mucins, we hypothesize that (1) the uncleavable attachment of known antigen sugar linkages could derive an immunostimulant glycosylation patterning in Muc7, and (2) the glycosylation of varying serine residues in the 23-mer peptide, in the tandem repeat region, could prove pertinent in immunostimulant properties in the Muc7. The C-linked glycosides being synthesized are the alpha-Ser-GlcNAc and alpha-Ser-GalNAc, with incorporation into the 23-mer by solid phase peptide synthesis (SPPS). The synthesis of the notable sugars is through a 6-step synthesis with the full characterization of all products utilizing 1D and 2D NMR, FTIR, and mass spectrometry. It is our goal to model and synthesize a series of Muc7 replicas, with non-cleavable carbon-carbon bond linkages to determine an active biological function. Specifically, we hypothesize that glycosylation of specific serine and threonine residues will sufficiently induce an oral immune function.

Additional Abstract Information