Applications of isotopes in advancing structural and functional heparanomics.

Heparanomics is the study of all the biologically active oligosaccharide domain structures in the entire heparanome and the nature of the interactions among these domains and their protein ligands. Structural elucidation of heparan sulfate and heparin oligosaccharides is a major obstacle in advancing structure-function relationships and heparanomics. There are several factors that exacerbate the challenges involved in the structural elucidation of heparin and heparan sulfate; therefore, there is great interest in developing novel strategies and analytical tools to overcome the barriers in decoding the enigmatic heparanome. This review focuses on the applications of isotopes, both radioisotopes and stable isotopes, in the structural elucidation of the complex heparanome at the disaccharide or oligosaccharide level using liquid chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry. This review also outlines the utility of isotopes in determining the substrate specificity of biosynthetic enzymes that eventually dictate the emergence of biologically active oligosaccharides.