Advanced glycosaminoglycan sequencing

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The interaction between proteins and cell-surface ligands underpin many biological processes such as cell growth, homeostasis, apoptosis and the ability of pathogens to invade host cells. One important family of cell surface ligands are the carbohydrate family of glycosaminoglycans (GAGs) found on the surface of almost all mammalian cells. Analysis of the sequence of the linear block-like arrangement of these GAGs is a significant technical challenge due to only miniscule quantities of pure material being (readily) available, poor chemistries and insensitive detection equipment. This research aims to develop and test a new method for sequencing these GAG polysaccharides utilising recent fundamental improvements made by the applicant. These developments include the exploitation of the opposite end of the molecule than is conventionally used (non-reducing end), with a vastly improved labelling mechanism and an advanced detection system for the conventional end of the molecule (reducing end). This approach will provide a powerful and sensitive sequencing technique capable of employing both ends of the GAG saccharide for characterization. The information gained from GAG sequencing will enable researchers to study previously elusive structures and processes that are biologically and medically significant.