Spiciarich, D. R., Nolley, R., Maund, S. L., Purcell, S. C., Herschel, J., Iavarone, A. T., Peehl, D. M., Bertozzi, C. R. Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding. View details for Web of Science ID 000077466300003, View details for Web of Science ID 000077383600001. Rodriguez-Rivera, F. P., Zhou, X., Theriot, J. She became an assistant professor at Berkeley in 1996 and a full professor of chemistry and molecular and cell biology in 2002. She described the reaction between the modified sugar and the fluorescent molecule as bioorthogonal. Grunwell, J. R., Rath, V. L., Rasmussen, J., Cabrilo, Z., Bertozzi, C. R. Discovery of sulfated metabolites in mycobacteria with a genetic and mass spectrometric approach. Here we review common enrichment strategies used in modern mass spectrometry (MS)-based glycoproteomic experiments, including lectins and other affinity chromatographies, hydrophilic interaction chromatography (HILIC) and its derivatives, porous graphitic carbon (PGC), reversible and irreversible chemical coupling strategies, and chemical biology tools that often leverage bioorthogonal handles. She also later developed a click reaction called the strain-promoted alkyne-azide cycloaddition, which, unlike other click reactions involving azides and alkynes, did not require toxic copper ions for the azide to snap together with the alkyne and was highly effective for tracking glycans in live cells. View details for Web of Science ID 000082564500003. These measurements show that the glycocalyx exhibits nanoscale organization on both cell lines and primary human tumor cells. We further developed a protein purification method that involves QC ligation of biotin to a protein of interest, capture on streptavidin resin, and finally release using only UV light. The increase of cell surface sialic acid is a characteristic shared by many tumor types. Here we describe a method for the site-specific introduction of aldehyde groups into recombinant proteins using the 6-amino-acid consensus sequence recognized by the formylglycine-generating enzyme. Glycomic and glycoproteomic analyses via microarrays and mass spectrometry are beginning to characterize alterations in glycans that correlate with disease. Laughlin, S. T., Agard, N. J., Baskin, J. M., Carrico, I. S., Chang, P. V., Ganguli, A. S., Hangauer, M. J., Lo, A., Prescher, J. Lin, F. L., van Halbeek, H., Bertozzi, C. R. Synthetic analogues of glycosylphosphatidylinositol-anchored proteins and their behavior in supported lipid bilayers. A combination of quantitative microscopy, mutational analysis, and interaction studies indicate that SteA and SteB form a complex that localizes to the cytokinetic ring to promote cell separation by RipC-FtsEX and may coordinate its PG remodeling activity with the biogenesis of other envelope layers during cell division. Such labeled proteins can then be treated with azide-functionalized probes to ligate affinity handles or fluorophores to the PKMT substrates. However, current data suggest that glycosylated mucin domains are created by the successive, often hierarchical, action of several specific ppGalNAcTs. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Even though we have only demonstrated its use in visualizing glycans, it can be envisioned that this probe could also be used for bioluminescence imaging of any azide-containing biomolecule, such as proteins and lipids, since azides have been previously incorporated into these molecules. View details for Web of Science ID 000171962100014. [16], Bertozzi completed her Ph.D. in chemistry at University of California, Berkeley in 1993 with Mark Bednarski, working on the chemical synthesis of oligosaccharide analogs. Using azide-modified molecular precursors of sialic acids and copper-free click chemistry, we visualized the spatiotemporal dynamics of the sialome in live zebrafish embryos. For N-glycopeptides, HCD and sceHCD generate similar numbers of identifications, although sceHCD generally provides higher quality spectra. We show that Glyco-seek detects attomoles of glycoproteins of interest from cell lysates, with sensitivity several orders of magnitude higher than that of current techniques. This report describes a general strategy for engineering the display of chemically defined oligosaccharides on cell surfaces that combines the concepts of metabolic engineering and selective chemical reactivity. View details for Web of Science ID A1995TD84500001. A., Qi, Y. n., Yasumoto, Y. n., Schmitz, C. O., Mumbach, M. R., Limaye, A. n., Wei, J. n., Alfajaro, M. M., Parker, K. R., Chang, H. Y., Horvath, T. L., Carette, J. E., Bertozzi, C. n., Wilen, C. B., Satpathy, A. T. Enhanced Bactericidal Effects of Pyrazinamide Toward Mycobacterium smegmatis and Mycobacterium tuberculosis upon Conjugation to a {Au(I)-triphenylphosphine}+ Moiety. Furthermore, the membrane-bound glycopolymers were internalized into early endosomes similarly to endogenous membrane components and were capable of specific interactions with protein receptors. She has found a smart way to connect cells together. View details for Web of Science ID 000259139900020, View details for PubMedCentralID PMC2721638. However, the specific glycoproteins that contribute to the cancer cell-surface sialylation are not well characterized, specifically in bona fide human disease tissue. In this work, we tested a panel of glycopolymers bearing a variety of lipids to identify those that persist on cell membranes. The C-type lectins dectin-1 and dectin-2 contribute to innate immunity against microbial pathogens by recognizing their foreign glycan structures. Andres, L. M., Blong, I. W., Evans, A. C., Rumachik, N. G., Yamaguchi, T., Pham, N. D., Thompson, P., Kohler, J. J., Bertozzi, C. R. Bioorthogonal Labeling of Human Prostate Cancer Tissue Slice Cultures for Glycoproteomics. Carol Bertozzi, a Stanford University chemist, won the Nobel Prize in chemistry in 2022. Similarly, the ability to perceive the spatial organization of glycans could transform our understanding of their role in development, infection, and disease progression. These findings suggest that high mannose glycans are the major component of cell surface glycosylation with even terminal glucoses. View details for PubMedCentralID PMC5675001. Here, we systematically explore the advantages and disadvantages of conventional HCD, sceHCD, ETD, and EThcD for intact glycopeptide analysis and determine their suitability for both N- and O-glycoproteomic applications. A critical branch point in mucin-type oligosaccharides is the beta 1-->3 glycosidic linkage to the core alpha-N-acetylgalactosamine (GalNAc) residue. Here we demonstrate that cell surfaces can be engineered to display synthetic bioactive polymers at defined densities by exogenous membrane insertion. Our study supports an essential role of one of the GalNAc-Ts - GALNT3, in EOC dissemination, including its implication in modulating PTMs and EOC metabolism. We previously described a chemical method to image glycans during zebrafish larval development; however, we were unable to detect glycans during the first 24 hours of embryogenesis, a very dynamic period in development. Using this approach quantities of homogeneous material were obtained for structural and functional analysis. Barb, A. W., Leavy, T. M., Robins, L. I., Guan, Z., Six, D. A., Zhou, P., Bertozzi, C. R., Raetz, C. R. Programmed assembly of 3-dimensional microtissues with defined cellular connectivity, Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Together with previous studies, these findings suggest that this redox cofactor may play a role in mycobacterial pathogenesis. She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. Marcaurelle, L. A., Mizoue, L. S., Wilken, J., Oldham, L., KENT, S. B., Handel, T. M., Bertozzi, C. R. Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens, Chemoselective elaboration of O-linked glycopeptide mimetics by alkylation of 3-ThioGalNAc, Ketone isosteres of 2-N-acetamidosugars as substrates for metabolic cell surface engineering, Chemical and biological strategies for engineering cell surface glycosylation, Sulfation of N-acetylglucosamine by chondroitin 6-sulfotransferase 2 (GST-5). Chen, X., Wu, P., Rousseas, M., Okawa, D., Gartner, Z., Zettl, A., Bertozzi, C. R. DNA-barcode directed capture and electrochemical metabolic analysis of single mammalian cells on a microelectrode array. Hybridization of complementary DNA sequences enabled the assembly of multicellular structures with defined cell-cell contacts. Thus, for applications of bioorthogonal chemistry in living systems, we built upon Wittig and Krebs' observation with the design of cyclooctyne reagents that react rapidly and selectively with biomolecule-associated azides. As part of the quest for new gold drugs, we have explored the efficacy of three gold complexes derived from the tuberculosis drug pyrazinamide (PZA), namely, the gold(I) complex [Au(PPh3)(PZA)]OTf (1, OTf = trifluoromethanesulfonate) and two gold(III) complexes [Au(PZA)Cl2] (2) and [Au(PZO)Cl2] (3, PZO = pyrazinoic acid, the metabolic product of PZA) against two mycobacteria, Mycobacterium tuberculosis and Mycobacterium smegmatis. IsoTaG is therefore an effective platform for identification of intact glycopeptides labeled by alkynyl or azido sugars and will facilitate further studies of the glycoproteome. Professor Carolyn Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface sugars important to human health and disease. Corrections? In this approach, metabolic labeling substrates containing bioorthogonal functional groups are provided to cells for incorporation into biopolymers by endogenous biosynthetic machinery. Redundancy of related family members and embryonic lethality both complicate genetic methods for deconvoluting functions of glycosyltransferases. We postulate that covalent modification and perhaps inhibition of various mitochondrial enzymes by palmitoyl-CoA could lead to the metabolic impairments found in obesity-related diseases. We show that both Rv1129c and the MCC enzymes are required for intracellular growth in macrophages and that the growth defect of MCC mutants is largely attributable to the degradation of host-derived cholesterol. From a panel of synthetic derivatives, we identified an azido GalNAc analog (N-azidoacetylgalactosamine, GalNAz) that is metabolized by numerous cell types and installed on mucin-type O-linked glycoproteins by the ppGalNAcTs. Here we report a method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a metabolic label. Hotsclaw, C. M., Sogi, K. M., Gilmore, S. A., Scheller, M. W., Leavell, M. D., Bertozzi, C. R., Leary, J. The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as one of the key virulence factors of Mycobacterium tuberculosis. Varki, A., Cummings, R. D., Aebi, M., Packer, N. H., Seeberger, P. H., Esko, J. D., Stanley, P., Hart, G., Darvill, A., Kinoshita, T., Prestegard, J. J., Schnaar, R. L., Freeze, H. H., Marth, J. D., Bertozzi, C. R., Etzler, M. E., Frank, M., Vliegenthart, J. F., Ltteke, T., Perez, S., Bolton, E., Rudd, P., Paulson, J., Kanehisa, M., Toukach, P., Aoki-Kinoshita, K. F., Dell, A., Narimatsu, H., York, W., Taniguchi, N., Kornfeld, S. Chemistry Is Central to Repairing Genes and Global Health: Reflections on the 2015 Nobel Prizes in Chemistry and Physiology or Medicine. Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. A., Bertozzi, C. R. Synthetic Trehalose Glycolipids Confer Desiccation Resistance to Supported Lipid Monolayers. Omissions? Genetic complementation experiments showed that each of the three pathways was able to recover the mutant in the absence of trehalose, even at elevated temperatures. The building block was incorporated into a synthetic peptide derived from the active site of a Mycobacterium tuberculosis sulfatase. Presented herein is the synthesis and evaluation of a bisubstrate analogue designed to inhibit estrogen sulfotransferase. We present a novel glycodendron prosthetic which can be site-selectively appended to recombinant proteins to create 'N-glycosylated' glycoprotein mimics. Bisphenol A (BPA) is a widely used plasticizer whose estrogenic properties may impact hormone-responsive disorders and fetal development. The resulting surfaces are then demonstrated to be able to capture up to three distinct types of living cells in specific locations. Likewise, branching from the linear chain reduced metabolic conversion. 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