Controlling Glycocalyx Remodeling: Structural and Biological Functions of Polyamide Based Proteoglycan Mimetics

Abstract

The cell surface glycans serve as recognition elements for many biological events, ranging from cell-cell to cell-pathogen interaction, immune cells activation to organ development. Hence, cell surface engineering is a stimulating biomedical and biotechnology research. Herein we report a versatile approach to mimic cell surface glycans on a peptide backbone. Our method is based on solid-state peptide synthesis of alternative conjugation of N-O-methyloxyamine composed amino acid and pegylated spacer to form polypeptide chain with the well-defined sequence. By incorporating fluorescent probe and phospholipids at one of the peptide chains, a functional cell-surface ligand was developed. These ligands are treated with carbohydrate scaffolds to obtain desire multivalent glycolipids. By varying the length of polypeptide chain, a comprehensive library of cell-surface anchoring glycoprobes were developed. We hypothesized that the balance between hydrophilic/hydrophobic moieties in the glycoprobes regulates the residence time of the molecules on cell surface. Using specific sugar scaffold on these glycoprobes, we proposed to demonstrate epithelial to mesenchymal transitions (EMTs) and its potential applications in wound healing