Complex carbohydrates or glycans are involved in almost every physiological or pathological process. Advances in understanding the biological roles played by glycans, along with the factors that influence or alter their functions will provid important avenues for the development of new therapeutics, and diagnostics. In recognition of opportunities to advance the impact of glycoscience on human health, we have assembled a team of five senior investigators that will work cooperatively on three related research projects to exploit unique capabilities of a Core to produce recombinant mammalian glycosyltransferases. The research projects will 1) study biochemical and structural aspects of glycosyltransferase to define their acceptor specificities at a molecular and structural level 2) exploit the enzymes in a novel chemoenzymatic approach to provide glycans for structure activity relationship studies, aid in the development of the next generation of glycan microarray and as analytical standards;3) develop sugar nucleotide donors modified by a chemical reporters to label subsets of glycoconjugates for visualization, capture and identification of glycans in cellular models of disease. The three projects have high synergy. Each requires a relatively large panel of glycosyltransferases that will be produced by a core. In addition, they will generate reciprocal knowledge and resources. Project 1 and 3 will perform complementary studies to uncover glycosyl acceptor specificities of glycosyltransferases. Information about glycosyl acceptor specificities of glycosyltransferases will be employed by Project 2 to prepare glycans that otherwise are not accessible by chemo-enzymatic synthesis. Project 2 will generate synthetic glycans that will be employed by Project 1 for in depth studies of glycosyl acceptor specificities. Structural studies by Project 1 will provide important information for project to design of sugar nucleotide donors modified with a chemical reporter for cellular studies in the context of human disease.
Glycans play key roles in almost every biological process and are involved in every major disease. In recognition of opportunities to advance the impact of glycoscience on human health, this program project will study important aspect of the enzymes that biosynthesize these important biopolymers. The enzymes will also be employed to synthesize glycans of biomedical importance and used to monitor glycan trafficking and analysis in the context of human disease.
|Praissman, Jeremy L; Willer, Tobias; Sheikh, M Osman et al. (2016) The functional O-mannose glycan on Î±-dystroglycan contains a phospho-ribitol primed for matriglycan addition. Elife 5:|
|Yu, Seok-Ho; Zhao, Peng; Sun, Tiantian et al. (2016) Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation. J Biol Chem 291:3982-9|
|Xiang, Yong; Karaveg, Khanita; Moremen, Kelley W (2016) Substrate recognition and catalysis by GH47 Î±-mannosidases involved in Asn-linked glycan maturation in the mammalian secretory pathway. Proc Natl Acad Sci U S A 113:E7890-E7899|
|Sutton, Dewey A; Yu, Seok-Ho; Steet, Richard et al. (2016) Cyclopropenone-caged Sondheimer diyne (dibenzo[a,e]cyclooctadiyne): a photoactivatable linchpin for efficient SPAAC crosslinking. Chem Commun (Camb) 52:553-6|
|Revoredo, Leslie; Wang, Shengjun; Bennett, Eric Paul et al. (2016) Mucin-type O-glycosylation is controlled by short- and long-range glycopeptide substrate recognition that varies among members of the polypeptide GalNAc transferase family. Glycobiology 26:360-76|
|Li, Xiuru; Martin, Sharon J H; Chinoy, Zoeisha S et al. (2016) Label-Free Detection of Glycan-Protein Interactions for Array Development by Surface-Enhanced Raman Spectroscopy (SERS). Chemistry 22:11180-5|
|Sun, Tiantian; Yu, Seok-Ho; Zhao, Peng et al. (2016) One-Step Selective Exoenzymatic Labeling (SEEL) Strategy for the Biotinylation and Identification of Glycoproteins of Living Cells. J Am Chem Soc 138:11575-82|
|Subedi, Ganesh P; Johnson, Roy W; Moniz, Heather A et al. (2015) High Yield Expression of Recombinant Human Proteins with the Transient Transfection of HEK293 Cells in Suspension. J Vis Exp :e53568|
|Bello, Claudia; Wang, Shuo; Meng, Lu et al. (2015) A PEGylated photocleavable auxiliary mediates the sequential enzymatic glycosylation and native chemical ligation of peptides. Angew Chem Int Ed Engl 54:7711-5|
|Vaidyanathan, Krithika; Wells, Lance (2014) Multiple tissue-specific roles for the O-GlcNAc post-translational modification in the induction of and complications arising from type II diabetes. J Biol Chem 289:34466-71|
Showing the most recent 10 out of 16 publications