We have been interested in synthesizing neoglycopeptide analogs of a 32-residue glycopeptide derived from VEGF, a protein implicated in tumor growth. The parent peptide is glycosylated by GlcNAc at Asn-27, and we have previously identified aptamers that selectively bind it. The desired analogs were designed to test the selectivity of the aptamer binding by varying the location of glycosylation between the native Asn locations (2 and 27) and the nature of the sugar. To ease the synthetic burden, we made our analogs using a strategy where we substituted one or both of the natural Asn residues with an amino acid containing an alkoxyamino side chain[1], which allows selective glycosylation at these sites after the synthesis of the completed peptide. Here we describe the synthesis of the amino acid derivative, its incorporation into the desired peptides using Fmoc-based solid phase peptide synthesis, and the details of the peptide glycosylations to yield the desired group of analogs. Our future work is to assess the selectivity of aptamers for these modified peptides versus the native VEGF peptide. [1] A Versatile Set of Aminooxy Amino Acids for the Synthesis of Neoglycopeptides Michael R. Carrasco* and and Ryan T. Brown The Journal of Organic Chemistry 2003 68 (23), 8853-8858 DOI: 10.1021/jo034984x

Synthesis of neoglycopeptide analogs of a glycosylated VEGF peptide

251st National Meeting (2016)

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