Exploring artificial metalloglycosidases as selective catalysts for the recognition and degradation of the sLex tetrasaccharide

Abstract

Small molecule recognition of carbohydrate moieties is a largely uncharted area of chemistry. Herein we report the use of metallopeptide-based scaffolds for sugar recognition and catalysis by application of a metalated fucose-binding peptide to remove cellular sLe^x antigen that has been linked to cellular adhesion and cancer metastasis. Catalytic assays against synthetic carbohydrates show preference of the metallopeptide for fucosyl- and galactose-containing carbohydrates, while MS-assays demonstrate metallopeptide mediated degradation of native sLe^x tetrasaccharide in solution. Cellular assays indicate that the metallopeptide can remove the antigen from the surface of an HL-60 leukemia cell line, demonstrating potential therapeutic utility for these metallopeptides as artificial metalloglycosidases.