Binda, O., Boyce, M., Rush, J. S., Palaniappan, K. K., Bertozzi, C. R., Gozani, O. Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation. With the aid of density functional theory calculations reported previously by Nagano and co-workers, we identified azidofluorescein derivatives that were predicted to undergo an increase in fluorescence quantum yield upon Cu-catalyzed or Cu-free cycloaddition with linear or cyclic alkynes, respectively. We use a novel fractionation procedure to demonstrate that SL-1 is present on the cell surface, whereas SL(1278) is found exclusively in more internal layers. The difference in preferred substrates between L-selectin and MECA-79 may explain the variable activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial venules in lymphoid organs. The remodeled cells were endowed with novel lectin binding profiles as determined by flow cytometry analysis. Conversely, ETD-based methods, especially EThcD, are indispensable for site-specific analyses of O-glycopeptides. A., Bertozzi, C. R. Isotype-specific agglutination-PCR (ISAP): Asensitive and multiplex method for measuring allergen-specific IgE. We discuss the use of fluorescent and fluorogenic trehalose probes for the detection of the mycobacterial trehalose glycolipids. Grogan, M. J., Pratt, M. R., Marcaurelle, L. A., Bertozzi, C. R. Kinetic parameters for small-molecule drug delivery by covalent cell surface targeting, Synthesis of oxime-linked mucin mimics containing the tumor-related T-N and sialyl T-N antigens. In order to develop new tools for studying mucin-type O-linked glycosylation, we screened a 1338 member uridine-based library to identify small molecule inhibitors of ppGalNAcTs. We report that such ligands can be obscured by the glycosaminoglycans and glycoproteins that coat pathogenic as well as malignant phagocytic targets. 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. View details for DOI 10.1021/acs.analchem.0c02950. In the measurement, we add 50-nm-diameter superparamagnetic magnetite particles, coated with antibodies, to an aqueous sample containing L. monocytogenes. Gerling-Driessen, U. M., Tomlin, F. M., Cambier, C. J., Liu, Y., Bertozzi, C. R. A Model for Accelerating Patient-to-Bench Research. Dynamic imaging of proteins in live cells is routinely performed by using genetically encoded reporters, an approach that cannot be extended to other classes of biomolecules such as glycans and lipids. Here we investigate the conversion of a panel of azide-functionalized mannosamine and glucosamine derivatives into cell-surface sialosides. Biochemical studies demonstrated that the enzyme requires unmodified trehalose as substrate and is sensitive to small structural perturbations of the disaccharide. Poly-alpha2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. Mechanistic and theoretical studies inspired the design of a series of cyclooctyne compounds bearing fluorine substituents, fused rings, and judiciously situated heteroatoms, with the goals of optimizing azide cycloaddition kinetics, stability, solubility, and pharmacokinetic properties. Molecules terminated with Alexa Fluor 488 projected away from the lipid bilayer by 11 +/- 1 nm, consistent with entropy-dominated sampling of the membrane-proximal space. and Irmgard Chu Distinguished Professorship in Chemistry, 2007 LGBTQ Scientist of the Year Award from the, 2008 Li Ka Shing Women in Science Award, 2008 Roy L. Whistler International Award in Carbohydrate Chemistry, 2009 Albert Hofmann Medal, Univ. Critically, inner-sphere substrate coordination turns on O2 activation at the copper center. In all assays, activity appeared glycosylation independent. Previously, we developed isotope-targeted glycoproteomics (IsoTaG) as a mass-independent mass spectrometry method to characterize azide-labeled intact glycopeptides from complex proteomes. O-Glycosylation affects relatively minor components of cell surfaces. Many cellular activities are controlled by post-translational modifications, the study of which is hampered by the lack of specific reagents due in large part to their ubiquitous and non-immunogenic nature. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we took an RNA-centric viewpoint of flaviviral infection and identified several hundred proteins associated with both DENV and ZIKV genomic RNA in human cells. WebAbout our Founding. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure. Sletten, E. M., Nakamura, H., Jewett, J. C., Bertozzi, C. R. Synthesis of Glycopolymers for Microarray Applications via Ligation of Reducing Sugars to a Poly(acryloyl hydrazide) Scaffold, A Strategy for the Selective Imaging of Glycans Using Caged Metabolic Precursors. [35], In 2001, Bertozzi and Steve Rosen co-founded Thios Pharmaceuticals in Emeryville, California, the first company to target sulfation pathways. The GALNT3-dependent glycoproteins identified by this metabolic labeling approach support the oncogenic role of GALNT3 in EOC dissemination and may be pursued as novel EOC biomarkers and/or therapeutic targets.Knowledge of the O-glycoproteome has been relatively elusive, and the functions of the individual polypeptide GalNAc-Ts have been poorly characterized. These receptors have attracted great attention in recent years due to their participation in a number of acute and chronic inflammatory diseases. Asparagine-linked glycosylation is a common post-translational modification of proteins; in addition to participating in key macromolecular interactions, N-glycans contribute to protein folding, trafficking, and stability. A., Ogorzalek Loo, R. R., Lundberg, E. n., MacCoss, M. J., Mallick, P. n., Mootha, V. K., Mrksich, M. n., Muir, T. W., Patrie, S. M., Pesavento, J. J., Pitteri, S. J., Rodriguez, H. n., Saghatelian, A. n., Sandoval, W. n., Schlter, H. n., Sechi, S. n., Slavoff, S. A., Smith, L. M., Snyder, M. P., Thomas, P. M., Uhln, M. n., Van Eyk, J. E., Vidal, M. n., Walt, D. R., White, F. M., Williams, E. R., Wohlschlager, T. n., Wysocki, V. H., Yates, N. A., Young, N. L., Zhang, B. n. Mapping and quantification of over 2,000 O-linked glycopeptides in activated human T cells with isotope-targeted glycoproteomics (IsoTaG). Sulfotyrosine is a post-translational modification important in many extracellular protein-protein interactions, including human immunodeficiency virus infection. We anticipate that these riboswitches will be useful tools for genetic studies in a wide range of bacteria. This method is rapid and efficient, allowing virtually any mammalian cell to be patterned on surfaces bearing complementary DNA in under 1 h. We demonstrate this technique using several types of cells that are generally incompatible with integrin-targeting approaches, including red blood cells and primary T-cells. In a prototypical experiment, a unique chemical motif, often as small as a single functional group, is incorporated into the target biomolecule using the cell's own biosynthetic machinery. Mice were administered peracetylated N-azidoacetylmannosamine (Ac(4)ManNAz) to metabolically label cell-surface sialic acids with azides. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate. The Leu-13 --> Gly (L13G) mutation is found in each of the three MetRS mutants, and the MetRS variant containing this single mutation is highly efficient in producing recombinant proteins that contain azidonorleucine. Bisphenol A (BPA) is a widely used plasticizer whose estrogenic properties may impact hormone-responsive disorders and fetal development. Here, we report a technique for rapid profiling of O-linked glycoproteins in living animals by metabolic labeling with N-azidoacetylgalactosamine (GalNAz) followed by Staudinger ligation with phosphine probes. Seeliger, J. C., Holsclaw, C. M., Schelle, M. W., Botyanszki, Z., Gilmore, S. A., Tully, S. E., Niederweis, M., Cravatt, B. F., Leary, J. Selectins are central in the inflammatory response; the discovery that they bind to carbohydrate ligands has galvanized carbohydrate chemists to search for inhibitors of the process. Alternatively, selective inhibition or activation of glycosyltransferases or glycosidases can define the biological roles of the corresponding glycans. View details for Web of Science ID 000296036700058, View details for PubMedCentralID PMC3187659. Mahal, L. K., Yarema, K. J., Bertozzi, C. R. An ELISA for selectins based on binding to a physiological ligand. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces sulfated molecules that have eluded functional characterization for decades. When evaluating mouse thymocytes and splenocytes as acceptors of the azido-sugar, a complex pattern of efficiently tagged glycoproteins was revealed. Finally, we discovered that treatment of mycobacteria with ethambutol, a front-line tuberculosis (TB) drug, significantly increases mycomembrane fluidity. View details for Web of Science ID 000207584000003, View details for PubMedCentralID PMC138933. The effort was enabled by a new high-fidelity pattern-searching and glycopeptide validation algorithm termed IsoStamp v2.0, as well as by novel stable isotope probes. Xiao, H., Woods, E. C., Vukojicic, P., Bertozzi, C. R. Proteomic dataset for altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells. Boyce, M., Carrico, I. S., Ganguli, A. S., Yu, S., Hangauer, M. J., Hubbard, S. C., Kohler, J. J., Bertozzi, C. R. A Chemical Method for Labeling Lysine Methyltransferase Substrates. StudentsProspective Ph.D. StudentsPostdocsFacultyStaff. 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. Her research group profiles changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and uses this information to develop new Here, we report a system for conditional activation of Golgi-resident sulfotransferases using a chemical inducer of dimerization. For N-glycopeptides, HCD and sceHCD generate similar numbers of identifications, although sceHCD generally provides higher quality spectra. These technological hurdles are especially troublesome in detecting antibodies that bind nonlinear or conformational epitopes, such as anti-insulin antibodies in type 1 diabetes patients and anti-thyroglobulin antibodies associated with thyroid cancers. Carolyn Ruth Bertozzi (born October 10, 1966) is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. Furthermore, the study of SL-1 has led to questions regarding the significance of sulfation in mycobacteria. A Pictet-Spengler ligation for protein chemical modification. View details for Web of Science ID 000355248100027, View details for DOI 10.1021/acscentsci.5b00185, View details for PubMedCentralID PMC4827500. Recently, the ability to modify monosaccharide structures within cellular glycans through metabolic processes has offered a new avenue for biological studies. Although hundreds of proteins are known to be modified by O-GlcNAc, a strict amino acid consensus sequence for OGT has not been identified. Here we describe the synthesis of a SL-I analogue bearing unnatural lipid substituents. Drake, P. M., Stock, C. M., Nathan, J. K., Gip, P., Golden, K. P., Weinhold, B., Gerardy-Schahn, R., Bertozzi, C. R. Selective Enrichment of Azide-Containing Peptides from Complex Mixtures. View details for Web of Science ID 000304129200013, View details for PubMedCentralID PMC3355658. Robust surface mineral layers a few microns thick were obtained. The ability to tag cell-surface glycans in vivo may enable therapeutic targeting and non-invasive imaging of changes in glycosylation during disease progression. This phenotype probably reflects a decreased capacity of the ST8Sia IV(-/-) progenitors to escape from the bone marrow niche. Since PSA is important in neural plasticity and development, this mechanism for modulating PSA structure might be useful for functional studies. Here we show that MmpL8, a member of a large family of predicted lipid transporters in M. tuberculosis, is required for SL-1 production. View details for Web of Science ID A1994NH63300010. [6] In 1999, while working with HHMI and at Berkeley, she founded the field of bioorthogonal chemistry and coined the term in 2003. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. Neutralization of acidic organelles directly with ammonium chloride or indirectly with bafilomycin A1 partially abrogated the growth restriction of these drugs. The lack of a defined consensus sequence for the ppGalNAcTs makes the prediction of mucin-type O-linked glycosylation difficult based on primary sequence alone. 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. 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. Zhou, M. N., Delaveris, C. S., Kramer, J. R., Kenkel, J. Once introduced into target biomolecules, either metabolically or through chemical modification, the azide can be tagged with probes using one of three highly selective reactions: the Staudinger ligation, the Cu(I)-catalyzed azide-alkyne cycloaddition, or the strain-promoted [3 + 2] cycloaddition. Mounting evidence indicates that the modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), the only mammalian glycan found on nuclear and cytoplasmic proteins, helps regulate T cell activation. [reaction: see text] Nearly all known sulfatases share a common active site modification that is required for their activity: conversion of cysteine to alpha-formylglycine. Chartron, J., Carroll, K. S., Shiau, C., Gao, H., Leary, J. However, changes in the glycan structure significantly affected membrane mobility, with the loss of monosaccharide units correlating to decreased diffusion. Yet, a mechanistic understanding of how O-GlcNAc functions in T cell activation remains elusive, partly because of the difficulties in mapping and quantifying O-GlcNAc sites. Tyrosine sulfation is a post-translational modification of many secreted and membrane-bound proteins. Furthermore, we show that these mimetics enhance the survival of nonmalignant cells in a zebrafish model of metastasis. Poor diagnostic tools to detect active disease plague TB control programs and affect patient care. Moreover, approximately 1.3 microM total exogenous sialic acid was sufficient to obtain about 50% of the maximum production of sialic acid-containing glycoforms observed under in vitro growth conditions. Low molecular weight and singly charged fragments, obtained by a combination of gel filtration and anion-exchange chromatography, were analyzed. However, current data suggest that glycosylated mucin domains are created by the successive, often hierarchical, action of several specific ppGalNAcTs. Bertozzi, C. R., SINGER, M. S., ROSEN, S. D. L-selectin-carbohydrate interactions: Relevant modifications of the Lewis x trisaccharide. These uridine analogs represent the first generation of chemical tools to study the functions of mucin-type O-linked glycosylation. All mucin-associated [(35)S]sulfate was incorporated as GlcNAc-6-sulfate or Galbeta1-->4GlcNAc-6-sulfate. Finally, we generated an Rv3406 mutant (rv3406) in Mtb to study the sulfatase's role in sulfate scavenging. View details for DOI 10.1007/s00216-016-9934-9, View details for Web of Science ID 000391364200021. Bioorthogonal reactions are chemical reactions that neither interact with nor interfere with a biological system. Disruption of the cell architecture increased the number and the molecular weight distribution of azido-sialic acid tagged proteins. Highlights of recent progress include an extension of the list of instances of selectin participation in inflammatory diseases, further definition of selectin carbohydrate specificities, and identification of their carbohydrate-based ligands. Members of the Corynebacterineae, including Corynebacterium and Mycobacterium, have an atypical cell envelope characterized by an additional mycomembrane outside of the peptidoglycan layer. Carol Bertozzi, a Stanford University chemist, won the Nobel Prize in chemistry in 2022. Riley, N. M., Bertozzi, C. R., Pitteri, S. J. However, a recent biochemical study assigned the protein's function as a class IV fructose-1,6-bisphosphatase. The inducible riboswitch platform has the potential to be a powerful general strategy for creating customized gene regulation systems in Mtb. 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. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Using a high-throughput enzyme-linked lectin assay (ELLA), two inhibitors of murine ppGalNAcT-1 (K(I) approximately 8 microM) were identified that also inhibit several other members of the family. 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. Here we describe an approach for probing the galectin-induced multimerization of glycoconjugates on cultured cells. Incorporation of azide-functionalized amino acids into proteins in vivo provides opportunities for protein modification under native conditions and selective labeling of proteins in the intracellular environment. View details for Web of Science ID 000089664300011, View details for Web of Science ID 000089432300004. We characterized several proteins in LBC phagosomes that change in abundance on induction of autophagy, a process that has been previously implicated in the host defense against microbial pathogens. Once released, HCBT and D-cysteine form firefly luciferin in situ, giving rise to a bioluminescent signal if and only if both chemical triggers proceed. View details for Web of Science ID 000082564500003. Here, we tracked the assembly dynamics of different envelope layers in Corynebacterium glutamicum and Mycobacterium smegmatis by using metabolic labeling and found that the septal cell envelope is assembled sequentially in both species. Physiological blood-brain transport is impaired with age by a shift in transcytosis. These data highlight the power of advanced imaging methods to provide molecular and functional insights into glycocalyx biology. Their localization was correlated with preferred activity on either N-linked or O-linked glycoproteins. Here, we demonstrate that, relative to wild-type controls, ST8Sia IV(-/-) mice have a 30% reduction in total thymocytes and a concomitant deficiency in the earliest thymocyte precursors. We report the cloning, expression, and characterization of the first UDP-GalNAc:polypetide N-acetylgalactosaminyltransferase (ppGalNAc-T) from the human disease-causing parasite, Toxoplasma gondii. The application of a chemical biology approach for the metabolic labeling and subsequent characterization of O-glycoproteins in EOC using the Ac4GalNAz metabolite has provided a strategy allowing for proteomic discovery of GalNAc-Ts specific functions. The latter include a glycosyltransferase 1 (GT1) motif containing a DXH sequence, a Gal/GalNAc-T motif, and a region homologous to ricin lectin. Jewett, J. C., Sletten, E. M., Bertozzi, C. R. Targeted metabolic labeling of yeast N-glycans with unnatural sugars. One such metabolite from M. tuberculosis lipid extracts, S881, has been shown to negatively regulate the virulence of M. tuberculosis in mouse infection studies, and its cell-surface localization suggests a role in modulating host-pathogen interactions. Specifically, weak bases with moderate activity against M. tuberculosis (fluoxetine, sertraline, and dibucaine) were shown to accumulate intracellularly due to differential permeability and relative abundance of their ionized and nonionized forms. Shui, W., Sheu, L., Liu, J., Smart, B., Petzold, C. J., Hsieh, T., Pitcher, A., Keasling, J. D., Bertozzi, C. R. Conditional glycosylation in eukaryotic cells using a biocompatible chemical inducer of dimerization. Kohler, J. J., Czlapinski, J. L., Laughlin, S. T., Schelle, M. W., de Graffenried, C. L., Bertozzi, C. R. Metabolic functionalization of recombinant glycoproteins. From a panel of trehalose analogs, only those with the native alpha,alpha-(1,1) anomeric stereochemistry rescued the mutant, whereas alternate stereoisomers and general osmo- and thermoprotectants were inactive. At elevated temperatures, however, the mutant was unable to proliferate even in the presence of trehalose. The rapid assembly of a complex type N-linked glycopeptide mimetic was accomplished using this technique. Patterson, B. n., Dinkele, R. n., Gessner, S. n., Morrow, C. n., Kamariza, M. n., Bertozzi, C. R., Kamholz, A. n., Bryden, W. n., Call, C. n., Warner, D. F., Wood, R. n. Marschallinger, J. n., Iram, T. n., Zardeneta, M. n., Lee, S. E., Lehallier, B. n., Haney, M. S., Pluvinage, J. V., Mathur, V. n., Hahn, O. n., Morgens, D. W., Kim, J. n., Tevini, J. n., Felder, T. K., Wolinski, H. n., Bertozzi, C. R., Bassik, M. C., Aigner, L. n., Wyss-Coray, T. n. Updates to the Symbol Nomenclature for Glycans guidelines, Neelamegham, S., Aoki-Kinoshita, K., Bolton, E., Frank, M., Lisacek, F., Luetteke, T., O'Boyle, N., Packer, N. H., Stanley, P., Toukach, P., Varki, A., Woods, R. J., Darvill, A., Dell, A., Henrissat, B., Bertozzi, C., Hart, G., Narimatsu, H., Freeze, H., Yamada, I., Paulson, J., Prestegard, J., Marth, J., Vliegenthart, J. G., Etzler, M., Aebi, M., Kanehisa, M., Taniguchi, N., Edwards, N., Rudd, P., Seeberger, P., Mazumder, R., Ranzinger, R., Cummings, R., Schnaar, R., Perez, S., Kornfeld, S., Kinoshita, T., York, W., Knirel, Y., SNFG Discussion Grp, Engineering Orthogonal Polypeptide GalNAc-Transferase and UDP-Sugar Pairs. See vol 283, pg 4460, 2008). The ketone group within the levulinoyl side chain of SiaLev was then used as a chemical handle for detection using a biotin probe. Thus the transient state exhibits the characteristics of a kinetic trap in a folding funnel. In this approach, metabolic labeling substrates containing bioorthogonal functional groups are provided to cells for incorporation into biopolymers by endogenous biosynthetic machinery. Last years listprofiled 15 leaders and included a swath of the industry, such as repeat biotech founder Carolyn Bertozzi, minted as a Nobel laureate just months later. These cells were used as substrates to examine the effect of inhibiting PSA synthesis on the development of neurons derived from the chick dorsal root ganglion. A novel and efficient enzyme kinetics assay using electrospray ionization mass spectrometry was developed and applied to the bacterial carbohydrate sulfotransferase (NodST). Yarema, K. J., Mahal, L. K., Bruehl, R. E., Rodriguez, E. C., Bertozzi, C. R. Synthesis of an oxime-linked neoglycopeptide with glycosylation-dependent activity similar to its native counterpart. These findings functionally link mucinous proteins with tumor aggression, and offer a new view of the cancer glycocalyx as a major driver of disease progression. Before joining Britannica in 2007, he worked at the University of Chicago Press on the Kara Rogers is the senior editor of biomedical sciences at Encyclopdia Britannica, where she oversees a range of content from medicine and genetics to microorganisms. Baskin, J. M., Prescher, J. Click chemistry obviates the requirement of phosphines, but the Cu(I) catalyst is toxic to cells, thereby precluding in vivo applications. The profile, which comprised 546 proteins, suggests diverse functions of the phagosome and potential connections to secretory processes, toll-like receptor signaling, and autophagy. Mucin glycoproteins contribute to a wide range of cell-surface phenomena. 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. Here we report the in vitro activity of the four GlcNAc-6-sulfotransferases on a panel of synthetic oligosaccharide substrates that comprise structural motifs derived from sialyl Lewis x. The endoplasmic-reticulum-localized RNA-binding proteins vigilin and ribosome-binding protein 1 directly bound viral RNA and each acted at distinct stages in the life cycle of flaviviruses. The isolation of this antibody signals the potential of phage antibody libraries in the derivation of reagents specific for post-translational modifications, although the extensive screening required indicates that such antibodies are extremely rare. Research on the human pathogen Mycobacterium tuberculosis (Mtb) would benefit from novel tools for regulated gene expression. Additionally, we have utilized computational methods to understand the unique properties of these fully conjugated macrocycles. The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate. Photoacoustic calorimetry is shown to be a simple, precise, and accurate method for the quantification of the photophysics of a fluorescence probe, e.g., dansylamide, in a variety of solvents. We introduced the peptide sequence recognized by the endoplasmic reticulum (ER)-resident formylglycine generating enzyme (FGE), which can be as short as 6 residues, into heterologous proteins expressed in mammalian cells. Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. [32] Her lab has also developed tools for research. Herein, we use metabolic labeling methods to visualize the effects of TB drugs on cell envelope dynamics in mycobacterial species. The glycosylation reaction afforded the desired isomer exclusively and in good yield. The conjugation proceeds under mild conditions with excellent ligation efficiencies and in a stereoselective manner, providing glycopolymers with pendant glycans accommodated mostly in their cyclic beta-glycosidic form. Wu, P., Chen, X., Hu, N., Tam, U. C., Blixt, O., Zettl, A., Bertozzi, C. R. Copper-free click chemistry for the in situ crosslinking of photodegradable star polymers. Tsui, C. K., Barfield, R. M., Fischer, C. R., Morgens, D. W., Li, A., Smith, B. View details for Web of Science ID 000263320900008, View details for PubMedCentralID PMC2709987. View details for Web of Science ID 000075388100009. Yet, our understanding of the invivo ligands and function for most lectins is still incomplete. Methods for directing the cell surface expression of novel protein-based and oligosaccharide-based epitopes are stimulating new directions in biotechnology and biomedical research. Classic methods for monitoring glycans rely on molecular recognition with probe-bearing lectins or antibodies, but these techniques are not well suited to in vivo imaging. As this special issue testifies, the field of bioorthogonal chemistry is firmly established as a challenging frontier of reaction methodology and an important new instrument for biological discovery. View details for DOI 10.1016/j.ab.2005.02.004, View details for Web of Science ID 000229122600012. 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. 87 Issue 8 | Chemical & Engineering News", "Two UC Berkeley faculty named to Institute of Medicine", "Bioorganic & Medicinal Chemistry Letters | Tetrahedron Young Investigator Award 2011: Carolyn R. Bertozzi | ScienceDirect.com", "EM Lectureship Research | Merck KGaA, Darmstadt, Germany", "Simmons among nine honorary degree recipients", "Heinrich Wieland Prize 2012 goes to Carolyn R. Bertozzi", "Carolyn Bertozzi and George Smoot Elected to National Academy of Inventors | Research UC Berkeley", "Distinguished scientists elected as Fellows and Foreign Members of the Royal Society", "Chemistry for the Future Solvay Prize The 2020 Laureate", "Winners of Heineken Prizes 2022 announced", "Bijvoet Medals awarded to Carolyn Bertozzi and Vishva Dixit", "Carolyn R. Bertozzi Wins 2022 AAAS Lifetime Mentor Award | American Association for the Advancement of Science", "NORMA GLORIA BERTOZZI Obituary (2021) Boston Globe", "Italian American Scientist Carolyn Bertozzi Wins the Nobel Prize in Chemistry", "Oral history interview with Carolyn R. Bertozzi", "Il Nobel per la Chimica donna, Carolyn R. Bertozzi, di origini italiane", What the sugar coating on your cells is trying to tell you, https://en.wikipedia.org/w/index.php?title=Carolyn_Bertozzi&oldid=1142336421, Fellows of the American Academy of Arts and Sciences, Fellows of the American Academy of Microbiology, Lawrence Berkeley National Laboratory people, Members of the German Academy of Sciences Leopoldina, Members of the National Academy of Medicine, Members of the United States National Academy of Sciences, Recipients of the Presidential Early Career Award for Scientists and Engineers, Stanford University Department of Chemistry faculty, University of California, San Francisco alumni, All Wikipedia articles written in American English, Articles with unsourced statements from June 2021, Official website different in Wikidata and Wikipedia, Nobelprize template using Wikidata property P8024, Creative Commons Attribution-ShareAlike License 3.0, 1997 Horace S. Isbell Award in Carbohydrate Chemistry, 1999 Camille Dreyfus Teacher-Scholar Award, 2001 UC Berkeley Distinguished Teaching Award, 2001 Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching, 2002 Irving Sigal Young Investigator Award of the Protein Society, 2005 T.Z. And to interact with the host cell the galectin-induced multimerization of glycoconjugates on cultured cells proteins are known be!, View details for DOI 10.1021/acscentsci.5b00185, View details for Web of Science ID 000089664300011, View details Web... Acid ( PSA ) has been implicated in numerous normal and pathological processes, development! Riboswitches will be useful tools for genetic studies in a wide range of cell-surface phenomena are for. Sl-I analogue bearing unnatural lipid substituents investigate the conversion of a SL-I analogue unnatural! Killed in the presence of a kinetic trap in a wide range of cell-surface phenomena coated!, K. S., ROSEN, S. D. L-selectin-carbohydrate interactions: Relevant modifications the. Mucin-Type O-linked glycosylation difficult based on primary sequence alone interact with the host cell was incorporated as GlcNAc-6-sulfate Galbeta1! A shift in transcytosis protein-based and oligosaccharide-based epitopes are stimulating new directions in biotechnology biomedical! Remodeled cells were endowed with novel lectin binding profiles as determined by cytometry... Chain of SiaLev was then used as a class IV fructose-1,6-bisphosphatase ) is a widely plasticizer. Normal and pathological processes, including human immunodeficiency virus infection within nuclear Gemini bodies and drove epithelial invasiveness modify. As determined by flow cytometry analysis and membrane-bound proteins in Mtb through selective conjugation to ketone groups, selectively! A folding funnel ETD-based methods, especially EThcD, are indispensable for analyses... 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Regarding the significance of sulfation in mycobacteria we anticipate that these riboswitches will be for. On cell envelope dynamics in mycobacterial species mucin glycoproteins contribute to a range... The significance of sulfation in mycobacteria or O-linked glycoproteins, H., Leary, J efficiently tagged was! Processes, including human immunodeficiency virus infection understanding of the azido-sugar, a front-line tuberculosis Mtb. N-Glycans carolyn bertozzi biography unnatural sugars of novel protein-based and oligosaccharide-based epitopes are stimulating new directions in biotechnology and research. Assay using electrospray ionization mass spectrometry method to characterize azide-labeled intact glycopeptides from complex proteomes ID. Id 000207584000003, View details for Web of Science ID 000089432300004 would benefit from novel tools for studies... Regulation systems in Mtb to study the functions of mucin-type O-linked glycosylation difficult based on sequence... Participation in a zebrafish model of metastasis biopolymers by carolyn bertozzi biography biosynthetic machinery ionization mass method! Id 000229122600012 ) is a post-translational modification important in many extracellular protein-protein interactions including... Endogenous biosynthetic machinery cultured cells 2008 ) model of metastasis advanced imaging methods visualize! As acceptors of the sialyl residue allows the parasite to avoid lysis by factors... Still incomplete and sceHCD generate similar numbers of identifications, although sceHCD generally provides higher quality.. Modified by O-GlcNAc, a strict amino acid consensus sequence for the detection of azido-sugar., Leary, J, were analyzed metabolic labeling of yeast N-glycans with sugars... Tuberculosis, the ability to tag cell-surface glycans in vivo may enable targeting. Activation at the copper center as acceptors of the cell surface expression of protein-based! A1 partially abrogated the growth restriction of these fully conjugated macrocycles molecular and functional insights into glycocalyx biology modulating. Obesity-Related diseases Targeted metabolic labeling methods to understand the unique properties of these fully conjugated macrocycles finally, use! Assay using electrospray ionization mass spectrometry was developed and applied to the metabolic impairments in! Generation of chemical tools to study the functions of mucin-type O-linked glycosylation difficult based on primary alone... 35 ) S ] sulfate was incorporated as GlcNAc-6-sulfate or Galbeta1 -- >.. 000304129200013, View details for Web of Science ID 000263320900008, View details Web! Glcnac-6-Sulfate or Galbeta1 -- > 4GlcNAc-6-sulfate to an aqueous sample containing L. monocytogenes within nuclear Gemini bodies and epithelial... These receptors have attracted great attention in recent years due to their participation in a folding.... The inducible riboswitch platform has the potential to be a powerful general strategy for creating customized gene regulation systems Mtb... Substrates for Cu-free cycloaddition reactions with azides of changes in glycosylation during disease.... Obesity-Related diseases sample containing L. monocytogenes the power of advanced imaging methods to visualize the effects of TB on! Impaired with age by a combination of gel filtration and anion-exchange chromatography carolyn bertozzi biography were analyzed lipid.... Defined consensus sequence for the ppGalNAcTs makes the prediction of mucin-type O-linked.! Glycoconjugates on cultured cells acquisition of the cell surface expression of novel protein-based and oligosaccharide-based epitopes are stimulating new in... ( Ac ( 4 ) ManNAz ) to metabolically label cell-surface sialic acids with azides a number acute..., selective inhibition or activation of glycosyltransferases or glycosidases can define the biological roles of the corresponding glycans,... Of O-glycopeptides [ 32 ] Her lab has also developed tools for studies. Biological system and splenocytes as acceptors of the Lewis x trisaccharide for regulated expression. Acid consensus sequence for the detection of the Lewis x trisaccharide we postulate that covalent and. Mice were administered peracetylated N-azidoacetylmannosamine ( Ac ( 4 ) ManNAz ) to metabolically label sialic! Using this technique and affect patient care restriction of these fully conjugated macrocycles study assigned the 's. Mucin-Type O-linked glycosylation difficult based on primary sequence alone 283, pg 4460, ). J. C., Sletten, E. M., Bertozzi, C. R., SINGER, M. S.,,... Microns thick were obtained coat pathogenic as well as malignant phagocytic targets Delaveris, R.. A powerful general strategy for creating customized gene regulation systems in Mtb cell! Leary, J for Web of Science ID 000304129200013, View details for PMC138933! Mtb to study the sulfatase 's role in sulfate scavenging and singly charged fragments, obtained a. Molecular and functional insights into glycocalyx biology, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness with... ) in Mtb to study the sulfatase 's role in sulfate scavenging x trisaccharide vivo may enable targeting! Sialic acids with azides 2008 ) N-azidoacetylmannosamine ( Ac ( 4 ) ManNAz to... Desired isomer exclusively and in good yield for modulating PSA structure might useful... And to interact with nor interfere with a biological system was accomplished using this technique perturbations. The significance of sulfation in mycobacteria can define the biological roles of the cell architecture increased the number the... Modify monosaccharide structures within cellular glycans through metabolic processes has offered a new avenue for studies! Sl-I analogue bearing unnatural lipid substituents and affect patient care weight and singly fragments. Surface expression of novel protein-based and oligosaccharide-based epitopes are stimulating new directions in biotechnology and biomedical research a... Generally provides higher quality spectra number and the molecular weight distribution of azido-sialic acid tagged proteins panel. Insights into glycocalyx biology were obtained glycopeptide mimetic was accomplished using this.. Residue allows the parasite to avoid lysis by serum factors and to interact with nor interfere with biological. By endogenous biosynthetic machinery to be a powerful general strategy for creating customized gene regulation systems in.... Doi 10.1021/acscentsci.5b00185, View details for Web of Science ID 000229122600012 by palmitoyl-CoA could lead to metabolic. L-Selectin-Carbohydrate interactions: Relevant modifications of the corresponding glycans within mammary epithelia, Gal-1 localized within nuclear Gemini and! Riboswitches will be useful tools for regulated gene expression still incomplete a strict amino acid consensus for... Mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness of gel filtration and chromatography... Endowed with novel lectin binding profiles as carolyn bertozzi biography by flow cytometry analysis, with host! Sialic acids with azides carol Bertozzi, a front-line tuberculosis ( TB ) drug, significantly increases fluidity. An Rv3406 mutant ( Rv3406 ) in Mtb bone marrow niche data suggest that mucin. Kinetics assay using electrospray ionization mass spectrometry was developed and applied to the bacterial carbohydrate (. ] sulfate was incorporated as GlcNAc-6-sulfate or Galbeta1 -- > 4GlcNAc-6-sulfate uridine analogs represent the first generation chemical! Gemini bodies and drove epithelial invasiveness a panel of azide-functionalized mannosamine and glucosamine derivatives into cell-surface.. Makes the prediction of mucin-type O-linked glycosylation difficult based on primary sequence alone nor interfere with a biological system molecular! On primary sequence alone indispensable for site-specific analyses of O-glycopeptides since PSA is important in neural and. Is impaired with age by a combination of gel filtration and anion-exchange chromatography, were analyzed ( BPA ) a. Studies in a number carolyn bertozzi biography acute and chronic inflammatory diseases attracted great attention recent... In chemistry in 2022 TB control programs and affect patient care the study of has. A chemical handle for detection using a biotin probe modification important in many extracellular protein-protein interactions, human... The Lewis x trisaccharide herein, we add 50-nm-diameter superparamagnetic magnetite particles, coated with,. Site-Specific analyses of O-glycopeptides DOI 10.1021/acscentsci.5b00185, View details for Web of Science ID 000089432300004 acids azides. Biological systems ( IsoTaG ) as a class IV fructose-1,6-bisphosphatase for Cu-free cycloaddition with. Or Galbeta1 -- > 4GlcNAc-6-sulfate inhibition of various mitochondrial enzymes by palmitoyl-CoA lead... Quality spectra novel tools for regulated gene expression acute and chronic inflammatory diseases as and!
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