We provide genetic and biochemical evidence for the activities of two proteins, Chp1 and Sap (corresponding to gene loci rv3822 and rv3821), that complete this pathway. 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. On the basis of these results, we propose possible pathways for 6-sulfo sialyl Lewis x biosynthesis and suggest that sulfation may be an early committed step. Senaratne, R. H., Mougous, J. D., Reader, J. R., Williams, S. J., Zhang, T., Bertozzi, C. R., Riley, L. W. Lipidomics reveals control of Mycobacterium tuberculosis virulence lipids via metabolic coupling. Both significantly outperform EThcD methods, indicating that ETD-based methods are not required for routine N-glycoproteomics. Together, localisation and association govern the assembly of complex glycans and thereby regulate interactions at the cell surface. Mucin glycoproteins contribute to a wide range of cell-surface phenomena. Using a panel of sulfated lactose (Galbeta1-->4Glc) neoglycolipids as substrates in direct binding assays, we found that 6',6-disulfolactose was the preferred structure for L-selectin, although significant binding to 6'- and 6-sulfolactose was observed as well. A Pragmatic Guide to Enrichment Strategies for Mass Spectrometry-based Glycoproteomics. View details for DOI 10.1073/pnas.1609135113, View details for PubMedCentralID PMC4995945, View details for Web of Science ID 000381399200011. The recently described O-glycoprotease OpeRATOR presents exciting opportunities for O-glycoproteomics. Malaker, S. A., Quanico, J., Romero, A. R., Pascal, Q., Kobeissy, F., Abou-louard, S., Tierny, D., Bertozzi, C. R., Fornier, I., Salzet, M. O-Pair Search with MetaMorpheus for O-glycopeptide Characterization. We have coexpressed a human GST-5 cDNA with a GlyCAM-1/IgG fusion protein in COS-7 cells and observed four-fold enhanced [(35)S]sulfate incorporation into this mucin acceptor. B., Bertozzi, C. R., Pitteri, S. J., Giaccia, A. J., Plevritis, S. K. Toward Point-of-Care Detection of Mycobacterium tuberculosis: A Brighter Solvatochromic Probe Detects Mycobacteria within Minutes. Palaniappan, K. K., Pitcher, A. However, current bioaerosol sampling approaches have reported low detection yields in sputum-positive TB cases. Marcaurelle, L. A., Pratt, M. R., Bertozzi, C. R. A new approach to mineralization of biocompatible hydrogel scaffolds: An efficient process toward 3-dimensional bonelike composites, Synthesis of a bisubstrate analogue targeting estrogen sulfotransferase. She coined the term bioorthogonal chemistry to Walton, E. M., Cronan, M. R., Cambier, C. J., Rossi, A., Marass, M., Foglia, M. D., Brewer, W., Poss, K. D., Stainier, D. R., Bertozzi, C. R., Tobin, D. M. A tension-mediated glycocalyx-integrin feedback loop promotes mesenchymal-like glioblastoma. Cyclooctyne reagents have now been used for labeling azide-modified biomolecules on cultured cells and in live Caenorhabditis elegans, zebrafish, and mice. A., Ge, Y. n., Gunawardena, J. n., Hendrickson, R. C., Hergenrother, P. J., Huber, C. G., Ivanov, A. R., Jensen, O. N., Jewett, M. C., Kelleher, N. L., Kiessling, L. L., Krogan, N. J., Larsen, M. R., Loo, J. Flynn, R. A., Belk, J. Living organisms produce hydrogen peroxide (H(2)O(2)) to kill invading pathogens and for cellular signaling, but aberrant generation of this reactive oxygen species is a hallmark of oxidative stress and inflammation in aging, injury, and disease. 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. To address this shortcoming, we have developed a robust, high-throughput compatible, click chemistry-based approach to identify small molecules that interfere with the palmitoylation of Ras, a high value therapeutic target that is mutated in up to a third of human cancers. Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. Shin, S., Chung, S., Sanii, B., Comolli, L. R., Bertozzi, C. R., De Yoreo, J. J. This work establishes a platform for the rational design of fluorogenic azide probes with spectral properties tailored for biological imaging. 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. One of the most abundant is sulfolipid-1 (SL-1), a tetraacyl-sulfotrehalose glycolipid. A., Mills, J. R., Roforth, M. M., Pittock, S. J., McKeon, A., Page, K., Wolf, W. A., Sanda, S., Speake, C., Greenbaum, C. J., Tsai, C. Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells. View details for DOI 10.1016/j.bmcl.2011.06.057, View details for Web of Science ID 000293884100004, View details for PubMedCentralID PMC3184767, View details for Web of Science ID 000293220600016, View details for PubMedCentralID PMC3184769. Sulfolipid-I (SL-I) is an abundant metabolite found in the cell wall of Mycobacterium tuberculosis that is comprised of a trehalose 2-sulfate core modified with four fatty acyl substituents. She coined the term "bioorthogonal chemistry" for chemical reactions compatible with living systems. DIFBO was so reactive that it spontaneously trimerized to form two asymmetric products that we characterized by X-ray crystallography. Zebrafish embryos were treated with an unnatural sugar to metabolically label their cell-surface glycans with azides. A., Kalscheuer, R., Bertozzi, C. R. Density Variant Glycan Microarray for Evaluating Cross-Linking of Mucin-like Glycoconjugates by Lectins, Direct observation of kinetic traps associated with structural transformations leading to multiple pathways of S-layer assembly. 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. Carol Bertozzi, a Stanford University chemist, won the Nobel Prize in chemistry in 2022. View details for DOI 10.1021/acsinfecdis.6b00106, View details for Web of Science ID 000388161300007. Surprisingly, the dibenzoselenacycloheptynes also abstracted hydrogen atoms from solvents such as THF or toluene, forming dibenzoselenacycloheptene products. [47] Lycia Therapeutics focuses on developing technology which utilizes lysosome-targeting chimeras (LYTACs). 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. Finally, mechanistic and structural data from sulfate-assimilation enzymes have revealed how M. tb controls the flux of sulfate in the cell. Unlike existing systems for controlling gene expression in Mtb, the riboswitch does not require the co-expression of any accessory proteins: all of the regulatory machinery is encoded by a short DNA segment directly upstream of the target gene. We disabled key enzymes required for each of the three pathways in M. smegmatis by allelic replacement. Both sceHCD and EThcD have been used with success in large-scale glycoproteomic experiments, but they each incur some degree of compromise. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. Rabuka, D., Hubbard, S. C., Laughlin, S. T., Argade, S. P., Bertozzi, C. R. Chemical technologies for probing glycans, A role for sulfation-desulfation in the uptake of bisphenol A into breast tumor cells. Further, we propose that the method reported here could find widespread use in investigating the functional consequences of O-GlcNAcylation. Kaushik, S., Barnes, J., Bainer, R. O., Sa, J. K., Woods, E. C., Kai, F., Przybyla, L., Lakins, J. N., Phillips, J. J., Nam, D., Bertozzi, C. R., Weaver, V. M. Is the Nobel Prize in Chemistry Having a Boston Red Sox Moment? Several unique mycomembrane glycolipids have been isolated and structurally characterized, but the underlying organization and dynamics of glycolipids within the cell envelope remain poorly understood. This template-driven mineralization technique provides an efficient approach toward bonelike composites with high mineral-hydrogel interfacial adhesion strength. Riley, N. M., Bertozzi, C. R., Pitteri, S. J. Concomitantly, a subpopulation of neural progenitor cells (NPCs) acquired an immature neuronal morphology and expressed early neuronal markers such as -III tubulin (TUJ1) and microtubule associated protein 2 (MAP2), phenotypes that took longer to manifest in the absence of OGT inhibition. Inducible genetic inhibition of angiogenesis and Vegf signaling during granuloma formation results in bacterial growth deficits. Tsai, C., Robinson, P. V., Spencer, C. A., Bertozzi, C. R. Amit, I., Baker, D., Barker, R., Berger, B., Bertozzi, C., Bhatia, S., Biffi, A., Demichelis, F., Doudna, J., Dowdy, S. F., Endy, D., Helmstaedter, M., Junca, H., June, C., Kamb, S., Khvorova, A., Kim, D., Kim, J., Krishnan, Y., Lakadamyali, M., Lappalainen, T., Lewin, S., Liao, J., Loman, N., Lundberg, E., Lynd, L., Martin, C., Mellman, I., Miyawaki, A., Mummery, C., Nelson, K., Paz, J., Peralta-Yahya, P., Picotti, P., Polyak, K., Prather, K., Qin, J., Quake, S., Regev, A., Rogers, J. We report a method for selective labeling, affinity enrichment, and identification of cell-surface glycoproteins. O-glycopeptides with a modified N-terminal residue, such as those generated by OpeRATOR, present several potential benefits, perhaps the most notable being de facto O-glycosite localization without the need of glycan-retaining fragments in MS/MS spectra. Conrad, R. M., Grogan, M. J., Bertozzi, C. R. Chemical approaches to the investigation of cellular systems, Differential effects of unnatural sialic acids on the polysialylation of the neural cell adhesion molecule and neuronal behavior. Bertozzi completed her undergraduate degree in Chemistry at Harvard University and her Ph.D. at UC Berkeley, focusing on the chemical synthesis of oligosaccharide analogs. Winans, K. A., King, D. S., Rao, V. R., Bertozzi, C. R. Engineering novel cell surface receptors for virus-mediated gene transfer. The nematode Caenorhabditis elegans is an excellent model organism for studies of glycan dynamics, a goal that requires tools for imaging glycans in vivo. Although the early steps in SL-1 biosynthesis are known, the machinery underlying the final acylation reactions is not understood. Biography. Using a recently described method (Mahal, L. K., Yarema, K. J., and Bertozzi, C. R. (1997) Science 276, 1125-1128), we delivered a uniquely reactive ketone group to endogenous cell surface sialic acid residues by treating cells with the ketone-bearing metabolic precursor N-levulinoylmannosamine (ManLev). Importantly, glycopolymers containing biologically relevant branched oligosaccharides, such as sialyl Lewis(x), as well as sulfated glycosaminoglycan-like epitopes can be readily prepared using our methodology. Malignancy is associated with altered expression of glycans and glycoproteins that contribute to the cellular glycocalyx. View details for Web of Science ID 000172448800001. These reactions possess extreme selectivity and biocompatibility, such that their participating reagents can form covalent bonds within richly functionalized biological systems--in some cases, living organisms. Kinase inhibitors blocked growth of cells with an N610 mutation. View details for DOI 10.1021/acs.joc.8b00625, View details for Web of Science ID 000439761100020. 56Carolyn Bertozzi 12 Bertozzi won the prize for studying the sugar coats of cells. [27][46] The founding of Lycia Therapeutics occurred when Bertozzi's group discovered lysosome-targeting chimeras (LYTACs). Here we present the first synthetic trehalose glycolipids capable of providing desiccation protection to membranes of which they are constituents. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events. She coined the term "bioorthogonal chemistry" for chemical reactions compatible with living systems. In this study, we describe the development of a high-throughput assay for OGT and use it to profile the specificity of the enzyme among a panel of peptide substrates. Isotopic recoding is achieved via metabolic incorporation of a defined mixture of N-acetylglucosamine isotopologs into N-glycans. Furthermore, the palmitoylation of endogenous proteins including H- and N-Ras could be easily detected using omega-alkynyl-palmitate as label in cultured HeLa, Jurkat, and COS-7 cells, and, promisingly, in mice. Bertozzi received a bachelors degree in chemistry from Harvard University in 1988 and a doctorate in the same subject from the University of California, Berkeley in 1993. PAPS is also the substrate for sulfotransferases that produce sulfolipids, putative virulence factors, in Mycobacterium tuberculosis such as SL-1. WebCarolyn R. Bertozzi. 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