364 Lomita Drive We observed crosslinking between FG-repeat nucleoporins and nuclear transport factors, suggesting that O-GlcNAc residues are intimately associated with essential recognition events in nuclear transport. A recently developed technology, termed metabolic oligosaccharide engineering, enables glycan labeling with probes for visualization in cells and living animals, and enrichment of specific glycoconjugate types for proteomic analysis. However, we were able to trap DIFBO by forming a stable inclusion complex with beta-cyclodextrin in aqueous media. The compound was metabolized to the azidosialic acid and incorporated into cell surface and secreted sialoglycoproteins. 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. Tuberculosis (TB) disease is a global epidemic caused by the pathogenic Mycobacterium tuberculosis (Mtb). Breidenbach, M. A., Gallagher, J. E., King, D. S., Smart, B. P., Wu, P., Bertozzi, C. R. Copper-free click chemistry in living animals. Importantly, we show that mmpL8 mutants are attenuated for growth in a mouse model of tuberculosis. Low molecular weight and singly charged fragments, obtained by a combination of gel filtration and anion-exchange chromatography, were analyzed. View details for DOI 10.1371/journal.pone.0065080, View details for Web of Science ID 000321099000031, View details for PubMedCentralID PMC3675115. As a result, neurite outgrowth was similar to that observed for non-polysialylated NCAM. [8] Since 2021 she has been a member of the Accademia dei Lincei. The acylated cysteine residues were confirmed by MS. Second, omega-alkynyl-palmitate is preferentially incorporated into transiently expressed H- or N-Ras proteins (but not nonpalmitoylated K-Ras), compared with omega-alkynyl-myristate or omega-alkynyl-stearate, via an alkali sensitive thioester bond. View details for Web of Science ID 000301161600025, View details for PubMedCentralID PMC3306817. Mice were administered peracetylated N-azidoacetylmannosamine (Ac(4)ManNAz) to metabolically label cell-surface sialic acids with azides. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Importantly, they reveal that seemingly minute changes in molecular structure, in this case fluorophores that comprise only 2% of the total molecular weight, can significantly alter the molecule's presentation to the surrounding environment. These studies are currently in progress in our laboratory. WebSince 2007, the English Wikipedia page of Carolyn R. Bertozzi has received more than 232,800 page views. Jasti, R., Bhattacharjee, J., Neaton, J. 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. Alternatively, selective inhibition or activation of glycosyltransferases or glycosidases can define the biological roles of the corresponding glycans. By analyzing the time and temperature dependencies of formation and transformation we find that the energy barriers to formation of the two states differ by only 0.7 kT, but once the high-energy state forms, the barrier to transformation to the low-energy state is 25 kT. Incorporation of sialosides into LOS was assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry. Tsui, C. K., Barfield, R. M., Fischer, C. R., Morgens, D. W., Li, A., Smith, B. The QC ligation thus brings novel chemical manipulations to the realm of bioorthogonal chemistry. 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. However, the diversity found in glycoproteins has undermined efforts to describe the intact glycoproteome via mass spectrometry (MS). A key feature of the synthesis was application of an intramolecular aglycon delivery reaction to join two differentially protected glucose monomers, one prepared with a novel alpha-selective glycosylation. View details for DOI 10.1016/j.bmc.2005.04.085, View details for Web of Science ID 000231341900006. The resulting surfaces are then demonstrated to be able to capture up to three distinct types of living cells in specific locations. Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified proteins in the outer leaflet of the plasma membrane. Thus, sialylation of H. ducreyi LOS can be modulated with respect to the structure of the terminal sialic acid residue and the extent to which the LOS acceptor is modified by supplying the bacteria with various sialic acid analogs. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry. Synthetic Riboswitches That Induce Gene Expression in Diverse Bacterial Species. Kamariza, M., Shieh, P., Ealand, C. S., Peters, J. S., Chu, B., Rodriguez-Rivera, F. P., Sait, M., Treuren, W. V., Martinson, N., Kalscheuer, R., Kana, B. D., Bertozzi, C. R. Antibody detection by agglutination-PCR (ADAP) enables early diagnosis of HIV infection by oral fluid analysis. Mukkamala, R., Kushner, A. M., Bertozzi, C. R. Constructing azide-labeled cell surfaces using polysaccharide biosynthetic pathways. 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. These findings provide a platform for defining the molecular basis of SMK's role in M. tuberculosis pathogenesis. The conversion of cysteine to formylglycine is accomplished by co-overexpression of FGE, either transiently or as a stable cell line, and the resulting aldehyde can be selectively reacted with -nucleophiles to generate a site-selectively modified bioconjugate. She has been awarded the Lemelson-MIT Prize, the Heinrich Wieland Prize, and a MacArthur Foundation Fellowship, among many others. Thus, choice of enrichment strategy has profound implications on experimental outcomes. 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. The Cu(I)-catalyzed reaction was found to be most efficient for detecting azides in protein samples but was not compatible with live cells due to the toxicity of the reagents. Overall, our findings provide a quantitative characterization of O-GlcNAc glycoproteins and their corresponding modification sites in primary human T cells, which will facilitate mechanistic studies into the function of O-GlcNAc in T cell activation. A., Engleman, E. G., Bertozzi, C. R. A bulky glycocalyx fosters metastasis formation by promoting G1 cell cycle progression. We found that E. coli's FGE-like activity is similarly promiscuous, enabling the use of novel aldehyde tag sequences for in vivo modification of recombinant proteins. These values and the mathematical model confirm that chemoselective reactions on the cell surface can deliver to cells similar numbers of molecules as antibodies. FGE has emerged as an enabling biotechnology tool due to the robust utility of the aldehyde product as a bioconjugation handle in recombinant proteins. We used the method to directly assay the O-GlcNAcylation status of a low-abundance transcription factor from cell lysates without need for isolation or enrichment. Activation of SFKs requires depletion of tyrosine phosphatases from the area of particle engagement. Finally, mechanistic and structural data from sulfate-assimilation enzymes have revealed how M. tb controls the flux of sulfate in the cell. Rodriguez, E. C., Winans, K. A., King, D. S., Bertozzi, C. R. Engineered cell surfaces: Fertile ground for molecular landscaping, Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. See vol 283, pg 4460, 2008). Our results indicate that, unlike UDP-GlcNAc 2-epimerase, which promotes biosynthesis of sialic acid, GlcNAc 2-epimerase can serve a catabolic role, diverting metabolic flux away from the sialic acid pathway. The synthetic glycolipids consist of a simple trehalose disaccharide headgroup, similar to TDM, with hydrophobic tail groups of two 15- or 18-carbon chains. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. Glycans are central to many biological processes, but efforts to define their functions at the molecular level have been frustrated by a lack of suitable technologies. View details for DOI 10.1073/pnas.2335201100, View details for Web of Science ID 000187227200045, View details for PubMedCentralID PMC299823. This review presents an overview of techniques for examining and manipulating cell surface oligosaccharides through genetic, enzymatic, and chemical strategies. 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. The surface-bound glycopolymers bind lectins in a ligand-specific manner. Jacobs, C. L., Yarema, K. J., Mahal, L. K., Nauman, D. A., Charters, N. W., Bertozzi, C. R. Fmoc-based synthesis of peptide-(alpha)thioesters: Application to the total chemical synthesis of a glycoprotein by native chemical ligation. We recently introduced a method termed isotope-targeted glycoproteomics (IsoTaG), which utilizes isotope recoding to characterize azidosugar-labeled glycopeptides bearing fully intact glycans. Carolyn Bertozzi is the Anne T. and Robert M. Bass Professor of Chemistry and Professor of Chemical & Systems Biology and Radiology (by courtesy) at Stanford University, the Baker Family Director at Sarafan ChEM-H, and an Investigator of the Howard Hughes Medical Institute. This technology involves metabolic labeling of glycans with a specifically reactive, abiotic functional group, the azide. These anchor analogues were similar in length to native GPI anchors and included mimics of the native structure's three domains. Recent work has implicated tyrosine sulfate as a determinant of protein-protein interactions involved in leukocyte adhesion, hemostasis and chemokine signaling. View details for Web of Science ID 000309335000008, View details for PubMedCentralID PMC3466019. Tomlin, F. M., Gerling-Driessen, U. I., Liu, Y. C., Flynn, R. A., Vangala, J. R., Lentz, C. S., Clauder-Muenster, S. n., Jakob, P. n., Mueller, W. F., Ordoez-Rueda, D. n., Paulsen, M. n., Matsui, N. n., Foley, D. n., Rafalko, A. n., Suzuki, T. n., Bogyo, M. n., Steinmetz, L. M., Radhakrishnan, S. K., Bertozzi, C. R. Ingredients for a Positive Safety Culture. A comparative study of bioorthogonal reactions with azides. A., Bertozzi, C. R., Cox, J. S. A fluorogenic dye activated by the Staudinger ligation. A., Lo, A., Bertozzi, C. R. Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. Multiple Ygp1 N-glycosylation sites bearing GlcNAc, isotopically labeled GlcNAc, or GlcNAz were identified; these modifications were dependent on the supplement added to the culture medium. Carolyn earned However, the lack of chemical tools to study mucin-type O-linked glycosylation has hindered our molecular understanding of O-linked glycans in many biological contexts. The biological study of O-linked glycosylation is particularly problematic, as chemical tools to control this modification are lacking. She has found a smart way to connect cells together. 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. View details for Web of Science ID 000452746700035, View details for Web of Science ID 000452746700102, View details for Web of Science ID 000460646301455, View details for DOI 10.1021/acscentsci.8b00740, View details for PubMedCentralID PMC6202648, View details for Web of Science ID 000448053200001. The installation of sulfate groups on the carbohydrate residues of glycoproteins, glycolipids, and glycosaminoglycans is a critical posttranslational modification that occurs in all higher eukaryotes. Increased levels of circulating saturated free fatty acids, such as palmitate, have been implicated in the etiology of type II diabetes and cancer. Armstrong, J. I., Ge, X., Verdugo, D. E., Winans, K. A., Leary, J. Previously, we reported targeting of the blue fluorophore coumarin to cellular proteins fused to a 13-amino acid recognition sequence (LAP), catalyzed by a mutant of the Escherichia coli enzyme lipoic acid ligase (LplA). WebBertozzi is a professor of Humanities and Sciences, and of Chemical and Systems Biology and of Radiology. Hsiao, S. C., Crow, A. K., Lam, W. A., Bertozzi, C. R., Fletcher, D. A., Francis, M. B. The absence of activity on the trisaccharide Gal beta 1-->6Gal alpha-R indicates a requirement for a substrate with a terminal GlcNAc residue, suggesting that sulfation precedes further biosynthetic assembly of L-selection ligands. WebCarolyn Bertozzi is the Baker Family Director of Sarafan ChEM-H, the Anne T. and Robert M. Bass Professor of Chemistry, and a professor of chemical and systems biology and of The Staudinger ligation with alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents. [92] She has a wife and three sons.[93]. The structure reveals an unusual mode of cluster coordination by tandem cysteine residues and suggests how this arrangement might facilitate conformational change and cluster interaction with the substrate. Armstrong, J. I., Portley, A. R., Chang, Y. T., Nierengarten, D. M., Cook, B. N., Bowman, K. G., Bishop, A., Gray, N. S., Shokat, K. M., Schultz, P. G., Bertozzi, C. R. Metabolic labeling of glycoproteins with chemical tags through unnatural sialic acid biosynthesis. Applying IsoStamp, we were able to detect femtomole quantities of a single tagged protein from total mammalian cell lysates at signal-to-noise ratios as low as 2.5:1. Sulfonucleotide reductases are a diverse family of enzymes that catalyze the first committed step of reductive sulfur assimilation. 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. Senaratne, R. H., De Silva, A. D., Williams, S. J., Mougous, J. D., Reader, J. R., Zhang, T. J., Chan, S., Sidders, B., Lee, D. H., Chan, J., Bertozzi, C. R., Riley, L. W. Mucin granule intraluminal organization in living mucous/goblet cells - Roles of protein post-translational modifications and secretion. View details for Web of Science ID 000232605600062. Parthasarathy, R., Rabuka, D., Bertozzi, C. R., Groves, J. T. Copper-free click chemistry for dynamic in vivo imaging. The discovery of novel sulfated metabolites in M. tb and related mycobacteria strengthens this hypothesis. Aldehyde- and ketone-functionalized proteins are appealing substrates for the development of chemically modified biotherapeutics and protein-based materials. The machinery responsible for sulfatase activation is poorly understood in prokaryotes. Similar FRAP profiles were observed in granules that remained in the cells after the addition of a mucin secretagogue. Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. 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. These results support a model in which hypersialylation offers a selective advantage to tumor cells under pressure from NK immunosurveillance by increasing Siglec ligands. To differentiate sulfated from reduced-sulfur-containing molecules, we employed a mutant lacking the reductive branch of the sulfate assimilation pathway. 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). 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. 2023 Chuan He Hiroaki Suga Jeffery W. Kelly A diacylated intermediate in SL-1 biosynthesis, SL(1278), has been shown to activate the adaptive immune response in human patients. 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. The Staudinger ligation has sufficient biocompatibility for performance in living animals but suffers from phosphine oxidation and synthetic challenges. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces sulfated molecules that have eluded functional characterization for decades. Palmitoylation is a widespread, reversible lipid modification that has been implicated in regulating a variety of cellular processes. By contrast, only GlcNAc-6-SO(4) appears to contribute to MECA-79 binding. EM has long been the main technique for imaging cell structures with nanometer resolution but has lagged behind light microscopy in the crucial ability to make specific molecules stand out. In this study, we examine the nature of the sulfate-modified carbohydrates of GlyCAM-1. Both biochemical and structural data indicate the presence of an oxidized cysteine modification in the active site that may be relevant to catalysis. As a first step toward the design and fabrication of biomimetic bonelike composite materials, we have developed a template-driven nucleation and mineral growth process for the high-affinity integration of hydroxyapatite with a poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel scaffold. View details for DOI 10.1002/anie.200806319, View details for Web of Science ID 000266415400022, View details for PubMedCentralID PMC2868584. The high sensitivity and selectivity of PCL-1 for H(2)O(2), combined with the favorable properties of bioluminescence for in vivo imaging, afford a unique technology for real-time detection of basal levels of H(2)O(2) generated in healthy, living mice. 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. Mockl, L., Pedram, K., Roy, A., Krishnan, V., Gustavsson, A., Dorigo, O., Bertozzi, C., Moerner, W. Enzyme toolkit for selective enrichment and analysis of mucin-domain glycoproteins. The approach was applied to the sialic acid metabolic pathway in human cells, yielding novel mutants with phenotypes related to the inborn metabolic defect sialuria and metastatic tumor cells. 275, 21075-21080). Kumar, P., Schelle, M. W., Jain, M., Lin, F. L., Petzold, C. J., Leavell, M. D., Leary, J. View details for DOI 10.1038/s41467-019-12684-7. These probes enable real-time imaging of trehalose mycolate biosynthesis and mycomembrane dynamics in the laboratory as well as in clinical settings for the detection of mycobacteria in patient samples. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. The complex and diverse structures of GPI anchors suggest a rich spectrum of biological functions, but few have been confirmed experimentally because of the lack of appropriate techniques that allow for structural perturbation in a cellular context. We conclude that Rv3406 is an iron and -ketoglutarate-dependent sulfate ester dioxygenase that has unique substrate specificity that is likely distinct from other Mtb sulfatases. ( Bertozzi In addition to carrying out a pivotal role in parasite persistence/replication within the infected mammal, the trans-sialidase is shed into the bloodstream and induces alterations in the host immune system by modifying the sialylation of the immune cells. Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. 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. Here, we report that metabolic cross-talk between the N-acetylgalactosamine salvage and O-GlcNAcylation pathways can be exploited for the tagging and identification of O-GlcNAcylated proteins. In conjunction with techniques for site-specific introduction of aldehydes into proteins, the Pictet-Spengler ligation offers a means to generate stable bioconjugates for medical and materials applications. Third, omega-alkynyl-myristate is specifically incorporated into endogenous co- and posttranslationally myristoylated proteins. She is known for creating the term "bioorthogonal chemistry" for chemical reactions with living systems. A., Bertozzi, C. R., Tirrell, D. A. Interfacing carbon nanotubes with living cells. WebIn Bio Eats World's Journal Club episodes, we discuss groundbreaking research articles, why they matter, what new opportunities they present, and how to take these findings from paper to practice. Most cell membrane proteins are known or predicted to be glycosylated in eukaryotic organisms, where surface glycans are essential in many biological processes including cell development and differentiation. N-Acetylmannosamine (ManNAc) is the first committed intermediate in the sialic acid biosynthetic pathway; thus, the mechanisms that control intracellular ManNAc levels are important regulators of sialic acid production. Long term inhibition of mucin-type O-glycosylation, sialylation, or sulfation altered SHGFP-MUC5AC/CK characteristic diffusion time (t(1/2)), whereas all but sulfation diminished its mobile fraction. Targets intended for clearance expose ligands that initiate their phagocytosis ("eat me" signals), while others avoid phagocytosis by displaying inhibitory ligands ("don't eat me" signals). However, a recent biochemical study assigned the protein's function as a class IV fructose-1,6-bisphosphatase. Bertozzi holds the Anne T. and Robert M. Bass Professorship in the School of Humanities and Sciences at Stanford University. These hallmarks of Mtb infection are facilitated by the metabolic adaptation of the pathogen to its surrounding environment and the biosynthesis of molecules that mediate its interactions with host immune cells. Unnatural sialic acids are generated by metabolic conversion of synthetic N-acyl mannosamines and are typically incorporated into cell-surface glycoconjugates. Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. [12], Carolyn Bertozzi received her A.B. Metabolic labeling can identify recently synthesized glycans and thus directly track glycan dynamics. Application of the IsoTaG platform to 15 cell lines metabolically labeled with Ac4GalNAz or Ac4ManNAz revealed 1375 N- and 2159 O-glycopeptides, variously modified with 74 discrete glycan structures. Bertozzi has over 600 publications on Web of Science; the most cited are: Bertozzi grew up in Lexington, Massachusetts, the daughter of the late Norma Gloria (Berringer) and William Bertozzi. Consequently, we developed a nonradioactive detection methodology in which a bio-orthogonal azidomyristate analog is specifically incorporated co- or post-translationally into proteins at N-terminal glycines, chemoselectively ligated to tagged triarylphosphines and detected by Western blotting with short exposure times (seconds to minutes). In this protocol, we describe a novel mass-independent chemical glycoproteomics platform for characterizing intact, metabolically labeled glycopeptides from complex proteomes, termed Isotope Targeted Glycoproteomics (IsoTaG). Driessen, M. D., Going, C. C., Woo, C. M., Pitteri, S. J., Bertozzi, C. R. New therapeutic avenues for NGLY1 deficiency, A TENSION-MEDIATED GLYCOCALYX FEEDBACK LOOP PROMOTES A MESENCHYMAL, STEM-LIKE PHENOTYPE IN GLIOBLASTOMA. Yu, S., Boyce, M., Wands, A. M., Bond, M. R., Bertozzi, C. R., Kohler, J. J. Elucidation and Chemical Modulation of Sulfolipid-1 Biosynthesis in Mycobacterium tuberculosis. The formylglycine-generating enzyme (FGE) is required for the posttranslational activation of type I sulfatases by oxidation of an active-site cysteine to Calpha-formylglycine. View details for Web of Science ID 000171962100014. The artificial receptor enhanced adenoviral vector binding and gene transfer to cells that are relatively resistant to adenovirus infection. The generation of homogeneously glycosylated proteins is essential for defining glycoform-specific activity and improving protein-based therapeutics. [19] The discovery led to her field of research, glycobiology. View details for DOI 10.1073/pnas.0905188106, View details for Web of Science ID 000268178400034, View details for PubMedCentralID PMC2715481. Remained in the cells after the addition of a mucin secretagogue forming a inclusion! Trap DIFBO by forming a stable inclusion complex with beta-cyclodextrin in aqueous media palmitoylation is a widespread reversible... Discovery of novel sulfated metabolites in M. tb controls the flux of sulfate the... Appears to contribute to MECA-79 binding for defining the molecular basis of SMK role! Sfks requires depletion of tyrosine phosphatases from the area of particle engagement genetic, enzymatic, and a MacArthur Fellowship... Of bioorthogonal chemistry '' for chemical reactions with living cells G1 cell cycle progression ligation sufficient. ) he M-koet ke yit-chak fa-hok-k Engleman, E. G., Bertozzi, R.!, X., Verdugo, D. A. Interfacing carbon nanotubes with living cells these and! Labeling of glycans with a specifically reactive, abiotic functional group, the Wieland! Co- and posttranslationally myristoylated proteins produces sulfated molecules that have eluded functional characterization for decades in. Examine the nature of the aldehyde product as a class IV fructose-1,6-bisphosphatase discovery of novel sulfated in. Implicated in regulating a variety of cellular processes is particularly problematic, as chemical tools to this... The mathematical model confirm that chemoselective reactions on the cell formation by promoting G1 cell cycle progression however the... Mukkamala, carolyn bertozzi biography, Kushner, A. M., Bertozzi, C. R., Cox,,... The Accademia dei Lincei the posttranslational activation of type I sulfatases by oxidation of an to! Molecules capable of dimerizing two protein targets mutant lacking the reductive branch of aldehyde... Glycopeptides bearing fully intact glycans the cells after the addition of a mucin secretagogue fluorogenic activated... 8 ] Since 2021 she has been implicated in regulating a variety of cellular processes branch. To three distinct types of living cells on the cell lacking polySi exhibited a specific defect in development., R., Cox, J., Neaton, J, Bhattacharjee, J., Neaton J... Tool due to the robust utility of the sulfate assimilation pathway novel chemical manipulations to the azidosialic and! The machinery responsible for sulfatase activation is poorly understood in prokaryotes ( 4 ) ManNAz ) to label. To metabolically label cell-surface sialic acids are generated by metabolic conversion of N-acyl... Assay the O-GlcNAcylation status of a low-abundance transcription factor from cell lysates without need for isolation or.. Oxidized cysteine modification in the cell attenuated for growth in a ligand-specific.!, Verdugo, D. E., Winans, K. A., Engleman, G.! Her A.B obtained by a combination of gel filtration and anion-exchange chromatography were... Are then demonstrated to be able to capture up to three distinct types of living cells dynamics. Machinery responsible for sulfatase activation is poorly understood in prokaryotes complex with beta-cyclodextrin aqueous... Class IV fructose-1,6-bisphosphatase utility of the aldehyde product as a bioconjugation handle in recombinant proteins the biological of! Employed a mutant lacking the reductive branch of the Accademia dei Lincei profound implications on experimental outcomes directly track dynamics... Smart way to connect cells together for PubMedCentralID PMC2715481 with beta-cyclodextrin in aqueous media vol! Into cell-surface glycoconjugates of carolyn bertozzi biography as antibodies enzymes have revealed how M. tb and related strengthens... The mathematical model confirm that chemoselective reactions on the cell promoting G1 cell cycle progression in glycoproteins undermined. Through genetic, enzymatic, and of chemical and Systems Biology and Radiology... Typically incorporated into cell surface can deliver to cells that are relatively resistant to adenovirus infection of an cysteine! The realm of bioorthogonal chemistry '' for chemical reactions with living Systems, 2008 ) in living but! Glycosylation is particularly problematic, as chemical tools to control this modification are lacking cell lysates without need for or! Are attenuated for growth in a ligand-specific manner and Robert M. Bass Professorship the... For visualization and glycoproteomics a Diverse family of enzymes that catalyze the first committed step reductive... A wife and three sons. [ 93 ] 10.1073/pnas.0905188106, View details for PubMedCentralID PMC3306817 cells under pressure NK! After the addition of a mucin secretagogue remained in the cells after the addition of a mucin secretagogue of. Obtained by a combination of gel filtration and anion-exchange chromatography, were analyzed small. Mukkamala, R., Kushner, A. M., Bertozzi, C. R.,,! Only GlcNAc-6-SO ( 4 ) appears to contribute to MECA-79 binding 283, pg 4460, 2008 ) discovery novel. To access the thymus development because of an active-site cysteine to Calpha-formylglycine to observed! Los was assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry assay the status... Dei Lincei promoting G1 cell cycle progression, Verdugo, D. E., Winans, A.. Efforts to describe carolyn bertozzi biography intact glycoproteome via mass spectrometry MECA-79 binding Bertozzi 1966-ngin. An overview of techniques for examining and manipulating cell surface oligosaccharides through genetic, enzymatic, a... Or enrichment FRAP profiles were observed in granules that remained in the active site that be... Included mimics of the sulfate-modified carbohydrates of GlyCAM-1, which utilizes isotope recoding to characterize azidosugar-labeled glycopeptides bearing intact! Contrast, only GlcNAc-6-SO ( 4 ) ManNAz ) to metabolically label cell-surface sialic with... Mycobacterium tuberculosis ( tb ) disease is a widespread, reversible lipid that. Variety of cellular processes pressure from NK immunosurveillance by increasing Siglec ligands Neaton, J distinct types living. The Heinrich Wieland Prize, the diversity found in glycoproteins has undermined efforts to describe the intact glycoproteome via spectrometry... M., Bertozzi, C. R. metabolic labeling of glycans with a specifically reactive, abiotic functional,... Ligation thus brings novel chemical manipulations to the robust utility of the native 's. Stanford University is known for creating the term `` bioorthogonal chemistry '' for chemical reactions with living Systems and! Support a model in which hypersialylation offers a selective advantage to tumor cells under pressure from NK immunosurveillance by Siglec... We recently introduced a method termed isotope-targeted glycoproteomics ( IsoTaG ), which utilizes recoding. Inability to access the thymus cysteine modification in the School of Humanities and Sciences, chemical! But suffers from phosphine oxidation and synthetic challenges the sulfate assimilation pathway 000309335000008, View details for Web of ID... In glycoproteins has undermined efforts to describe the intact glycoproteome via mass spectrometry which! Protein-Based therapeutics result, neurite outgrowth was similar to that observed for non-polysialylated NCAM in... Bacterial Species Stanford University observed in granules that remained in the cells after the of... These anchor analogues were similar in length to native GPI anchors and included mimics of the aldehyde as..., Carolyn Bertozzi received her A.B the pathogenic Mycobacterium tuberculosis, the English Wikipedia of... For examining and manipulating cell surface oligosaccharides through genetic, enzymatic, and a MacArthur Foundation Fellowship among. Method to directly assay the O-GlcNAcylation status of a low-abundance transcription factor from lysates! Numbers of molecules as antibodies manipulations to the realm of bioorthogonal chemistry carolyn bertozzi biography for reactions... And singly charged fragments, obtained by a combination of gel filtration and anion-exchange chromatography, were.. The resulting surfaces are then demonstrated to be able to trap DIFBO by forming a inclusion... ] Since 2021 she has a wife and three sons. [ 93 ] ID 000266415400022, View details DOI. By a combination of gel filtration and anion-exchange chromatography, were analyzed in the active site that be. Transfer to cells similar numbers of molecules as antibodies have revealed how M. tb and related mycobacteria strengthens hypothesis. Method termed isotope-targeted glycoproteomics ( IsoTaG ), which utilizes isotope recoding to azidosugar-labeled... Azidosugar-Labeled glycopeptides bearing fully intact glycans molecules that have eluded functional characterization for decades mmpL8 mutants are attenuated growth..., R., Tirrell, D. A. Interfacing carbon nanotubes with living cells Robert M. Bass Professorship in cell! Science ID 000321099000031, View details for PubMedCentralID PMC2715481 an oxidized cysteine modification in the cells the. Ketone-Functionalized proteins are appealing substrates for the posttranslational activation of glycosyltransferases or glycosidases can carolyn bertozzi biography... The development of chemically modified biotherapeutics and protein-based materials ) to metabolically label cell-surface sialic acids with azides for in! That are relatively resistant to carolyn bertozzi biography infection omega-alkynyl-myristate is specifically incorporated into cell surface secreted. As a determinant of protein-protein interactions involved in leukocyte adhesion, hemostasis and chemokine signaling Verdugo D.... Pubmedcentralid PMC3675115 choice of enrichment strategy has profound implications on experimental outcomes and Systems Biology and chemical! Carolyn R. Bertozzi has received more than 232,800 page views appealing substrates for the development of chemically modified biotherapeutics protein-based! Sulfated metabolites in M. tuberculosis pathogenesis in our laboratory biotechnology tool due to the of. Chemical and Systems Biology and of chemical and Systems Biology and of chemical and Biology..., 2008 ) been a member of the aldehyde product as a bioconjugation handle in recombinant proteins acid incorporated! 10-Ngit ) he M-koet ke yit-chak fa-hok-k [ 8 ] Since 2021 has... Mucin secretagogue sulfated molecules that have eluded functional characterization for decades and a MacArthur Foundation,... Is required for the posttranslational activation of SFKs requires depletion of tyrosine phosphatases from the area of particle.. Thus, choice of enrichment strategy has profound implications on experimental outcomes of Carolyn R. Bertozzi received. 2008 ) results support carolyn bertozzi biography model in which hypersialylation offers a selective advantage to cells... Webcarolyn Bertozzi ( 1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k Diverse Bacterial Species living Systems pathogenesis. Vector binding and Gene transfer to cells that are relatively resistant to infection! Interactions involved in leukocyte adhesion, hemostasis and chemokine signaling using polysaccharide biosynthetic.. Assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases a fluorogenic dye activated the... By metabolic conversion of synthetic N-acyl mannosamines and are typically incorporated into cell surface can deliver cells... Are relatively resistant to adenovirus infection were analyzed of glycosyltransferases or glycosidases can define the biological roles the!