Synthesis of a heparin-related GlcN–IdoA sulfation-site variable disaccharide library and analysis by Raman and ROA spectroscopy.

Synthesis of an array of differentially sulfated GlcN–IdoA disaccharides, accessible on good scale, directly from L-iduronate components is described. These are specifically directed to provide the sulfation vari- ability at the key most common biologically relevant sulfation-variables L-IdoA O-2 and D-GlcN O-6 and amino sites of this heparin disaccharide. This sulfation-varied matrix has allowed the first evaluation of using Raman/ROA spectroscopy to characterize changes in spectra as a function of both site and level of sulfation with pure, defined heparin-related disaccharide species. This provides analysis of both similar- ities and differences to digest native heparin and this shows evidence of different types of changes in con- formations and conformational freedom as a function of some specific sulfation changes at the disaccharide level. It is anticipated that this data set will open the way for applications to further site-spe- cific sulfated saccharides and demonstrates the capability offered by Raman–ROA towards fingerprinting sulfation in heparin fragments.