Mucin-type O-gly co sy la tion is initiated by a large family of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAc Ts) that transfer GalNAc from UDP-GalNAc to the Ser and Thr residues of polypeptide acceptors. [9] View details for Web of Science ID A1995TG85900001. We designed a 4-N,N-dimethylamino-1,8-naphthalimide-conjugated trehalose (DMN-Tre) probe that undergoes >700-fold increase in fluorescence intensity when transitioned from aqueous to hydrophobic environments. View details for DOI 10.1016/j.ab.2005.02.004, View details for Web of Science ID 000229122600012. To obtain structural information about these biomolecules, and the modifications they may undergo during different stages of cell growth and development, a mass spectrometry-based method was developed and used to obtain unambiguous structural information on the glycosaminoglycans (GAGs) that comprise heparin/HS. Given the sensitivity and negligible background provided by bioluminescence imaging (BLI), we reasoned that 1 might be able to overcome some of the limitations encountered with fluorescent phosphine probes. Using RAFT polymerization, we synthesized well-defined glycopolymers (GPs) functionalized with galectin-binding glycans along the backbone, a lipid group on one end and a fluorophore on the other. Genomic and proteomic profiling form a basis for biological discovery. Chemical reactions that enable selective biomolecule labeling in living organisms offer a means to probe biological processes in vivo. The average clinical sensitivity and specificity were 96% and 97%. These data show that the normal distribution of surface glycosylation requires IL-1R, but not MyD88, and is not sufficient to prevent bacterial binding. The challenge of engineering glycosylation has been confronted by synthetic chemists, biochemists and cell biologists, each with the primary goal of optimizing glycoconjugates for therapeutic applications. Their reactive carbonyl groups are typically conjugated with -effect nucleophiles, such as substituted hydrazines and alkoxyamines, to generate hydrazones and oximes, respectively. One leads directly to the final low-energy state and the other to the kinetic trap. A microtiter plate assay for UDP-galactopyranose mutase, an essential cell wall biosynthetic enzyme of Mycobacterium tuberculosis, was developed. Ngo, J. T., Adams, S. R., Deerinck, T. J., Boassa, D., Rodriguez-Rivera, F., Palida, S. F., Bertozzi, C. R., Ellisman, M. H., Tsien, R. Y. This reaction has a second-order rate constant of 0.25 M(-1) s(-1), on par with fast bioorthogonal reactions of azides, and proceeds readily in aqueous environments. Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. The galectin family of glycan-binding proteins is thought to mediate many cellular processes by oligomerizing cell surface glycoproteins and glycolipids into higher-order aggregates. View details for Web of Science ID 000392525600001, View details for PubMedCentralID PMC5255568. Carolyn R. Bertozzi is the 550th most popular chemist, the 15,732nd most popular biography from United States and the 111th most popular American Chemist. The successful integration of living cells into synthetic devices requires precise control over cell patterning. The glycan symbol nomenclature proposed by Harvey et al. Densely O-glycosylated mucin domains are found in a broad range of cell surface and secreted proteins, where they play key physiological roles. View details for Web of Science ID 000430563200441. Our findings suggest that differential glycosylation at the level of tissue microanatomy regulates the nuclear function of Gal-1 in the context of mammary gland morphogenesis and in cancer progression. Muia, R. P., Yu, H., Prescher, J. View details for DOI 10.1016/j.ceb.2004.06.007, View details for Web of Science ID 000223130800003. Nijmegen) (2013); Elected Fellow of the National Academy of Inventors (2013); Heinrich Wieland Prize (2012); Elected member of the Institute of Medicine (2011); Tetrahedron Young Investigator Award for Bioorganic and Medicinal Chemistry (2011); Royal Society of Chemistry - Organic Division, Bioorganic Chemistry Award (2010); Lemelson-MIT Prize (2010); Albert Hofmann Medal, Univ. This study introduces a technique for the rapid profiling and quantitation of N- and O-glycans on cell membranes using membrane enrichment and nanoflow liquid chromatography/mass spectrometry of native structures. View details for DOI 10.1016/j.jasms.2006.08.010, View details for Web of Science ID 000244109300001, View details for PubMedCentralID PMC2755055. Work in our laboratory led to the development of two bioorthogonal transformations that exploit the azide as a small, abiotic, and bioinert reaction partner: the Staudinger ligation and strain-promoted azide-alkyne cycloaddition. Although the chemical reporter strategy has been used in conjunction with bioorthogonal chemistry to image the external glycosylation state of live zebrafish and detect tumor-associated glycans in mice, the ability to image glycans systemically within a live organism has remained elusive. Goon, S., Schilling, B., Tullius, M. V., Gibson, B. W., Bertozzi, C. R. GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism. The trend noted with solvent polarity is different and more revealing than that determined by the more classical approach of examining either the wavelength of the emission maximum or the fluorescence quantum yield. Two approaches that emphasize developing selective methods to dissect, modify, and control receptor-ligand interactions at the cellular interface are discussed. View details for Web of Science ID 000296036700058, View details for PubMedCentralID PMC3187659. 275, 21075-21080). Xiao, H., Woods, E. C., Vukojicic, P., Bertozzi, C. R. Proteomic dataset for altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells. An unnatural derivative of N-acetyl-mannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. (2001) Glycobiology 11, 11R-18R]. We synthesized two unnatural oligosaccharide substrates, GlcNAc beta 1-->6Gal alpha-R and Gal beta 1-->4GlcNAc beta 1-->6Gal alpha-R, that incorporate structural motifs from the native L-selection ligands into an unnatural C-glycosyl hydrocarbon scaffold. The synthetic glycolipids consist of a simple trehalose disaccharide headgroup, similar to TDM, with hydrophobic tail groups of two 15- or 18-carbon chains. Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment. The importance of nonclassical, multistage crystallization pathways is increasingly evident from theoretical studies on colloidal systems and experimental investigations of proteins and biomineral phases. View details for Web of Science ID 000082757300015. Furthermore, DMN-Tre labeling was reduced by treatment with TB drugs, unlike the clinically used auramine stain. View details for DOI 10.1016/j.chembiol.2004.05.009, View details for Web of Science ID 000222987300018, View details for DOI 10.1002/cbic.200300789, View details for Web of Science ID 000220196800018. In 2014, it was announced that Bertozzi would lead ACS Central Science, the American Chemical Society's first peer-reviewed open access journal, which offers all content free to the public. Such genetic engineering in combination with stable isotopic labeling can be applied to various metabolic pathways and their products. View details for DOI 10.1371/journal.pgen.1008284. This story was updated on Wednesday, Oct. 6, at 1:23 p.m. PDT. Chemically tunable mucin chimeras assembled on living cells. A Bioorthogonal Reaction of N-Oxide and Boron Reagents. To validate our results, we employed gel shift assays based on conjugating mass tags to O-GlcNAc groups. The staggering complexity of glycans renders their analysis extraordinarily difficult, particularly in living systems. Her lab focuses on profiling changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and exploiting this information for development of diagnostic and therapeutic approaches, most recently in the area of immuno-oncology. View details for DOI 10.1021/acs.joc.8b00625, View details for Web of Science ID 000439761100020. Using these probes, chemoselective imaging of either H(2)O(2) or caspase 8 activity was performed in vitro and in vivo. Chartron, J., Carroll, K. S., Shiau, C., Gao, H., Leary, J. The FGE recognition sequence, or aldehyde tag, can be inserted into heterologous recombinant proteins produced in either prokaryotic or eukaryotic expression systems. Sulfotransferases catalyze the transfer of a sulfuryl group from the eukaryotic sulfate donor 3'-phosphoadenosine 5'-phosphosulfate to an acceptor biomolecule. We report herein the chemical synthesis and preliminary mechanistic investigation of diptericin, an 82 residue glycopeptide that contains regions similar to two different types of antibacterial peptides. Site-specific characterization of glycosylation requires intact glycopeptide analysis, and recent efforts have focused on how to best interrogate glycopeptides using tandem mass spectrometry (MS/MS). The cell surface contains a wealth of information that determines how cells interact with their environment. Chung, S., Shin, S., Bertozzi, C. R., De Yoreo, J. J. Difluorobenzocyclooctyne: Synthesis, Reactivity, and Stabilization by beta-Cyclodextrin. WebCarolyn Ruth Bertozzi (born October 10, 1966) is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. This study reports the vaccine potential of an attenuated 5'-adenosine phosphosulfate reductase mutant (DeltacysH) of M. tuberculosis. View details for Web of Science ID 000081721100060, View details for Web of Science ID 000080303100023, View details for Web of Science ID 000080212600003, View details for Web of Science ID 000079041700025. View details for DOI 10.1016/j.bmcl.2011.05.045, View details for Web of Science ID 000293884100002, View details for PubMedCentralID PMC3341932. Lin, F. L., Hoyt, H. M., van Halbeek, H., Bergman, R. G., Bertozzi, C. R. Synthetic glycopeptides and glycoproteins as tools for biology, Functional hydrogel-biomineral composites inspired by natural bone, Azido sialic acids can modulate cell-surface interactions, A small-molecule switch for Golgi sulfotransferases. The artificial receptor enhanced adenoviral vector binding and gene transfer to cells that are relatively resistant to adenovirus infection. Kinetic analysis of the mutants identified residues that are essential for catalytic activity. She coined the Cohen, A. S., Dubikovskaya, E. A., Rush, J. S., Bertozzi, C. R. Visualizing enveloping layer glycans during zebrafish early embryogenesis. We report a non-destructive biochemical technique, termed "Glyco-seek", for analysis of O-GlcNAcylated proteins. She is an elected member of the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. We developed a poly(acryloyl hydrazide) (PAH) scaffold to which we conjugated a variety of reducing glycans ranging in structure from simple mono- and disaccharides to considerably more complex human milk and blood oligosaccharides. In this study we have examined how unnatural sialic acids can alter polysialic acid expression and influence the adhesive properties of the neural cell adhesion molecule (NCAM). Beatty, K. E., Williams, M., Carlson, B. L., Swarts, B. M., Warren, R. M., van Helden, P. D., Bertozzi, C. R. Synthesis and Reactivity of Dibenzoselenacycloheptynes. Cioce, A., Bineva-Todd, G., Agbay, A. J., Choi, J., Wood, T. M., Debets, M. F., Browne, W. M., Douglas, H. L., Roustan, C., Tastan, O. Y., Kjaer, S., Bush, J. T., Bertozzi, C. R., Schumann, B. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Assimilatory 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductases are evolutionarily related, homologous enzymes that catalyze the same overall reaction, but do so in the absence of an [Fe-S] cluster. Additionally, we exploited the photolability of the QC ligation product to render the adduct cleavable with a handheld UV lamp. Imbert, P. R., Saric, A. n., Pedram, K. n., Bertozzi, C. R., Grinstein, S. n., Freeman, S. A. Electron-Based Dissociation Is Needed for O-Glycopeptides Derived from OpeRATOR Proteolysis. This review summarizes current efforts to obtain homogeneous glycopeptide and glycoprotein materials by a variety of methods that draw from the techniques of recombinant expression, chemical synthesis, enzymatic transformation, and chemoselective ligation. 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