Chapter 13 - Protein Glycosylation: An Important Tool for Diagnosis or Early Detection of Diseases

Abstract

Proteins are highly dynamic diverse cellular entities regulating all cellular functions. Translated from transcripts, nascent peptides undergo posttranslational modifications (PTMs). Although these modifications impart important characteristic features to the proteins, the unusual modification pattern of some proteins also lead to their loss/gain in functions leading to disorders. Studies on protein modifications are expected to establish potential suitable biomarkers useful for diagnosis and early detection of diseases. Glycosylation is one of the most important PTMs of proteins, which plays an essential role in various biological processes. In fact, alterations in glycosylation are associated with many diseases and, thus, act as promising targets and biomarkers for monitoring health conditions. Understanding the exact mechanism contributing to altered glycoproteomes in specific diseases is very important to advance our molecular knowledge of the underlying pathogenesis. Over the last few years, revolutionary advances in “omics” technologies have highlighted the progressive need to restructure traditional approaches to basic and clinical research in order to facilitate the rapid, efficient integration and translation of these new technologies into novel effective therapeutics. The recent advances in mass spectrometry (MS) instrumentation, combined with innovative peptide fractionation and protein/peptide tagging have advanced our understanding of the complex and dynamic nature of proteomes and opened the way for reliable and high-throughput characterization of protein PTMs. Due to their heterogeneous nature, development of rapid and sensitive methods for analysis of aberrant glycoproteins associated with diseases has become critical. MS has become a powerful tool for the determination of chain length and composition of monosaccharide classes, whereas linkage information and monosaccharide identification are usually deduced using gas chromatography (GC) (after chemical derivatization) or NMR. In order to enable high-throughput analysis of a complex glycome, these complimentary techniques are often used together. Thus, with the availability of the maturing glycoproteomics technologies and their potential to provide unique structure-based insight into glycobiology, comparative glycoproteomics strategies may be applied for development of accurate biomarkers and targeted therapeutics toward the investigated pathologies. This chapter provides an overview of the technologies and their applications in identification of abnormal glycoproteins and glycans, and considers the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes.