Facile Synthesis of O-Glycans and O-Glycopeptides

Georgia State University, Atlanta GA

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Abstract

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. This proposal is developing core synthesis ? enzymatic extension (CSEE) approach to produce large glycans and glycopeptides with most natural structural diversity. In CSEE approach, a core comprising a few sugars in the reducing end is synthesized first. Convergent core synthesis is cost-efficient with well documented methodologies. Then glycosyltransferases are used to elongate the core by following a variety of different biosynthesis pathways to generate complex and larger glycoconjugates with high diversity. Depending on high region- and stereo-selectivity of glycosyltransferases, CSEE is the most efficient approach to produce complex glycoconjugates with high fidelity. Our recent success of using 7 chemically synthesized N-glycan cores and 4 glycosyltransferases to produce 73 complex N-glycans clearly demonstrates that CSEE is an answer to the complexity and diversity of glycomes. In this program, 8 cores of O-GalNAc-Ser/Thr will be synthesized and extended with 16 glycosyltransferases to afford focused and diverse O-GalNAc-glycans/glycopeptides libraries; 3 cores of O-Man-Ser/Thr will be synthesized and extended with 9 glycosyltransferase to produce O-Man glycans/glycopeptides; O-Fuc, O-Glc and O-Xyl glycans and glycopeptides will be produced similarly. CSEE for synthesis of these O-glycan/O-glycopeptides will be fully validated in other labs. The technology advance of this proposal is to automate the enzymatic extension by using a conventional peptide synthesizer. We will fully investigate stability and optimal reaction conditions for the most synthetic useful glycosyltransferases and make the information accessible via a website. In summary, this program should make such a dream come true: scientists can have affordable access to any N- & O-glycans and glycopeptides as they have for regular peptides.