The proposed research program applies Solidus technology in microarraying, biocatalysis, and screening and the Linhardt group's expertise in heparin/heparan sulfate to the field of glycomics. Glycomics, the comprehensive study of glycan structure-function relationship, is a sub-discipline of metabolomics and the next step beyond genomics and proteomics. Heparin glycosaminoglycans (heparin and heparan sulfate) are among the most structural complex biopolymers. These glycans carry and store significant biological information crucial in virtually all pathological and pathophysiological processes involving cell-cell interaction and communication.
The specific aims and milestones of this Phase I STTR proposal are to: 1. prepare a heparin glycan microarray; 2. probe this microarray with the highly specific heparin-binding protein, antithrombin III; 3. prepare an enzyme-modified heparosan microarray; 4. probe this microarray with a collection of heparin-binding proteins to examine binding specificity; and 5. prepare a structurally defined glycan microarray based on the glycosyltransferase extension, and enzymatic modification of heparosan oligosaccharide acceptors for probing with heparin-binding proteins. Phase I will focus on developing the core technology required for developing a HepGly chip as a glycomics platform for screening interactions with heparin-binding proteins. Potential applications for a HepGly microarray include the development of the next generation of heparin-based drugs, the evaluation small molecule drugs that antagonize with heparin/heparan sulfate interaction with heparin-binding proteins and the rapid screening of biological samples in diagnostic applications. A phase II proposal will be prepared to develop these commercial applications. ? ? ?
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