Discovery of glucose-specific, peptide-based carbohydrate mimics using phage displayed random peptide libraries.

Phage displayed random peptide libraries were used to discover peptides which functionally mimic the monosaccharide glucose by screening these libraries against glucose-specific lectins. Although the screening of phage display libraries against single lectins has been previously reported, debate exists whether the resulting peptides are indeed true sugar mimics or merely act as ligands for the targeted lectin. As part of a larger project to establish general rules for peptide and peptidomimetic-based sugar mimicry, we have screened two phage display libraries (“C-X7-C” and “X12”) against a series of three glucose-binding plant lectins: Concanavalin A (Con A), Pisum Sativum Agglutinin (PSA), and Lens Culinaris Agglutinin (LCA), so as to discover ligands that bind ALL THREE lectins and therefore could act as true functional sugar mimics. Because screening for sets of targets is a novel strategy, screens were performed in a number of optimized formats. The resulting peptide CSPIYKDTC strongly bound to Con A at the sugar binding site and bound weakly to LCA and PSA, indicating that it may be a functionally mimicking glucose. General rules for peptide and peptidomimetic-based sugar mimicry was established. It is hoped that it is possible to employ a similar strategy to find mimics of other monosaccarides, such as mannose )Man) or galactose (Gal) or more complex carbonhydrates.Master of Scienc