Molecular Evidence of Glycosylation Effect on the Peptide Assemblies Identified with Scanning Tunneling Microscopy

Abstract

Glycosylation not only plays a functional role in biological events, but also significantly affects physicochemical properties of proteins. Glycoprotein MUC1 with a variable number of tandem repeats (VNTRs) serves as a promising target for immunotherapy of epithelial cancer. Herein, we synthesized the pristine VNTR and glycosylated VNTR with T antigen functionalized Thr₉ and Tn antigen modified Ser₁₅, involving both disaccharide and monosaccharide. The pristine peptides and glycopeptides are observed to form homogeneous assemblies on the highly oriented pyrolytic graphite surfaces by using scanning tunneling microscopy. These peptide assemblies down to the molecular level demonstrate pronounced site-specific instability induced by glycosylation on graphite surface. Moreover, it can be recognized that disaccharide exerts greater influence on the stability of peptide assemblies than monosaccharide. These results could contribute to the structural insights of glycoprotein and pertinent design of biological applications