Synthesis and preliminary comparative structure-function studies of glycosylated and non-glycosylated analogues of a thrombin inhibitory peptide, variegin

Abstract

Glycosylation is a well known post-translational modification of eukaryotic proteins. The precise structural effects of glycosylation on protein back bone and its correlation with the protein function is still a less understood aspect. In the present study, we tried to address this problem using thrombin protein and a recently discovered thrombin inhibitory glycopeptide Variegin. As the identity of the sugar in this peptide is not known, we have synthesized two β linked O-glycosylated variegins along with the non-glycosylated analogue and their structure-function studies were carried out using circular-dichroism spectroscopy and thrombin time assay. No conclusive differences were observed between β-glucosylated, β-galactosylated and non-glycosylated variegins as indicated by their secondary structures and thrombin time assay. Thus it necessitates the synthesis of a wide variety of glycosylated analogues besides using more sensitive techniques and sophisticated assays to point out the structural and functional effects of glycosylation on peptide. However, our study introduces a new working model system to study the structural effects of protein glycosylation.