Abstract/Summary

Sialic acids are a family of over 50 derivatives of neuraminic acid that are widely available in Nature and that play many biological roles in health and disease. They are generally located at the terminus of glycans, which in turn form part of glycoproteins and glycolipids. N-Acetyl neuraminic acid (Neu5Ac), the most abundant sialic acid, has been hypothesised to be a biomarker for various diseases including cardiovascular disease (CVD). The presence of many diseases, including CVD can be linked to an increase in plasma and serum concentration of Neu5Ac in disease patients versus healthy controls. Increased Neu5Ac concentrations in plasma have also been linked to increased risk of CVD mortality. These studies have been limited in scope, studying only one derivative of sialic acid and only in plasma and serum. Multiple isomers of acetylated sialic acid exist, challenges have been encountered in synthesising these compounds however, which has hampered impact in this area. Given that Neu5Ac is associated with multiple diseases we need more precise biomarkers for diseases such as CVD. Therefore, the research described here aimed to investigate acetylated sialic acid derivatives as biomarkers for CVD and CVD mortality risk, not only in plasma and serum, but also in urine and saliva. Overall, the work carried out in this thesis details the utility of synthetic sialic acid derivatives as quantitative standards for the analysis of plasma, serum, urine, and saliva. The biomarker potential of Neu5Ac and Neu5,9Ac2 for CVD risk and the presence of advanced CVD was also evaluated.