DEVELOPMENT & UTILIZATION OF A MUCIN-GLYCOPEPTIDE MICROARRAY

University Of Georgia, Athens GA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Because mucin domains are components of a number of cell surface molecules, and recognition of these structures are important in cellular development and disease, we are interested in developing efficient methods for identifying their partners and interactions. Structural characteristics of the underlying scaffold of mucin glycoproteins in the display of pendant glycan epitopes are important. Therefore, to quantitatively characterize their interactions, relevant glycoconjugate constructs are needed rather than isolated glycans. Our goal is to address the requirement through development of a microarray platform that will allow rapid screening for partners. Availability of such constructs has been a limitation in such studies. We have adopted an approach based on glycopeptide chemical synthesis, providing well-defined structures, which can be further elaborated biochemically. In developing a robust array, novel linkers and ligation approaches are being developed and evaluated for anchoring glycopeptides to the slide. The initial selection of molecules will display truncated glycans as found in tumor associated glycoproteins. Details of molecular display on the array will be evaluated using monoclonal and polyclonal antibodies to printed structures. Systematic variation of the glycosylation on the glycoconjugates resulting from our chemical approach will allow definition of the selectivity of the interactions. This will be extended to screening of patient serum samples to investigate applications to detection of antibody cancer biomarkers. The project brings together the expertise in chemical synthesis and structural analysis at the CCRC at the University of Georgia, and glycan related array expertise at the Glycomics Center at Emory University.