We explored whether unnatural cell surface sialosides produced by metabolism can act as neo-antigens and modulate the immunogenicity of cells.Immunization of rabbits with synthetic conjugates of an unnatural sialic acid bound to keyhole limpet hemocyanin produced significant titers of antibodies that were specific for the structurally altered sialic acid. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Cell surface carbohydrates mediate interactions between the cell and its environment. The dependence of the desiccation protection on the synthetic trehalose glycolipid fraction is nearly identical to that of TDM. View details for DOI 10.1002/anie.201504249, View details for DOI 10.1021/jacs.5b04279, View details for Web of Science ID 000360321100003, View details for DOI 10.1021/acscentsci.5b00275, View details for PubMedCentralID PMC4827550. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. We investigated how the major phosphatase CD45 is excluded from contact sites, using single-molecule tracking. In this episode, Stanford Professor Carolyn Bertozzi and host Lauren Richardson discuss the article "Lysosome-targeting chimaeras for degradation of 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. Bertozzi is a member of the Royal Society and the academies of sciences of Germany and the United States. Among her many honours are the Lemelson-MIT Prize (2010), the Arthur C. Cope Award of the American Chemical Society (2017), and the Wolf Prize in Chemistry (2022). A., Gray, M. A., Bertozzi, C. R., Rabuka, D., Bassik, M. C. Quantitative super-resolution microscopy of the mammalian glycocalyx. Formylglycine generating enzyme (FGE) recognizes a pentapeptide consensus sequence, CxPxR, and it specifically oxidizes the cysteine in this sequence to an unusual aldehyde-bearing formylglyine. 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). By micropatterning IgG, the ligand of Fc receptors, we found that the barrier extended well beyond the perimeter of the receptor-ligand engagement zone. View details for DOI 10.1073/pnas.0900717106, View details for Web of Science ID 000264522600009, View details for PubMedCentralID PMC2660766. One such development is creating chemical tools for studying glycans in living systems. Using this approach, we identify 133 N-glycosites spanning 58 proteins, nearly doubling the number of experimentally observed N-glycosites in the yeast proteome. Malaker, S. A., Pedram, K. n., Ferracane, M. J., Bensing, B. WebBio BIO 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. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. This technique has attracted significant attention recently for the synthesis of biological macromolecules of defined homogeneous composition, the design of self-assembling drugs and the chemical remodeling of cell surfaces. Siegrist, M. S., Whiteside, S., Jewett, J. C., Aditham, A., Cava, F., Bertozzi, C. R. Strategy for Dual-Analyte Luciferin Imaging: In Vivo Bioluminescence Detection of Hydrogen Peroxide and Caspase Activity in a Murine Model of Acute Inflammation. Other sulfonucleotide reductases from structurally divergent subclasses appear to use the same mechanism, suggesting that this family of enzymes has evolved from a common ancestor. Furthermore, the same junctional peptidoglycan also serves as a mechanical link holding the daughter cells together and undergoes mechanical fracture during V snapping. A., Bertozzi, C. R., Gibson, B. W. A small-molecule modulator of poly-alpha 2,8-sialic acid expression on cultured neurons and tumor cells. Here, we show that increasing sialylated glycans on cancer cells inhibits human natural killer (NK) cell activation through the recruitment of sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7). In the present study, we expressed Rv2131c heterologously and found that the protein dephosphorylates PAP in a magnesium-dependent manner, with optimal activity observed between pH 8.5 and pH 9.5 using 0.5 mM MgCl 2. The ability to access glycopeptides of this type through chemical synthesis will facilitate further mechanistic studies. Gerling-Driessen, U. M., Tomlin, F. M., Cambier, C. J., Liu, Y., Bertozzi, C. R. A Model for Accelerating Patient-to-Bench Research. Polysialyltransferases catalyze the glycosylation of the neural cell adhesion molecule (NCAM) with polysialic acid (PSA). Furthermore, many biological studies would be aided by the ability to assemble biomolecules under physiological conditions. The advantage of this ELISA over previous assays is that a macromolecular physiological ligand is employed, rather than a fortuitous or simplified carbohydrate ligand. Williams, S. J., Senaratne, R. H., Mougous, J. D., Riley, L. W., Bertozzi, C. R. A 96-well dot-blot assay for carbohydrate sulfotransferases, Sulfotransferases and sulfatases in mycobacteria. ScTyrY43G and MmPheT413G label overlapping but distinct proteomes in human cell lines, with broader proteome coverage upon their coexpression. Furthermore, we demonstrate that SL-1 plays a role in mediating the susceptibility of Mtb to a human cationic antimicrobial peptide in vitro, despite being dispensable for maintaining overall cell envelope integrity. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces sulfated molecules that have eluded functional characterization for decades. These results establish the foundation for further development of BPDA-based colorimetric sensors. Against random peptide substrates, ppGalNAc T10 revealed no significant hydrophobic or hydrophilic residue enhancements, in contrast to what has been reported previously for ppGalNAc T1 and T2. To our knowledge, this is the first detailed mechanistic data reported for Stf0, which further demonstrates the power of mass spectrometry in elucidating the reaction pathway and catalytic mechanism of promising enzymatic systems. View details for Web of Science ID 000177054900001, View details for Web of Science ID 000175790100030, Here we report a concise stereoselective synthesis of myo-inositol via ring-closing metathesis. Using rational prediction analysis to recognize putative internal myristoylation sites in caspase-cleaved proteins combined with our nonradioactive chemical detection method, we identify 5 new post-translationally myristoylatable proteins (PKC epsilon, CD-IC2, Bap31, MST3, and the catalytic subunit of glutamate cysteine ligase). 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. Beam-type collisional activation, i.e., higher-energy collisional dissociation (HCD), has been a valuable approach, but stepped collision energy HCD (sceHCD) and electron transfer dissociation with HCD supplemental activation (EThcD) have emerged as potentially more suitable alternatives. 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. View details for DOI 10.1021/acs.jproteome.6b01053. Random mutagenesis yielded the best JamB variant with 20-fold increased activity in E. coli. View details for DOI 10.1016/j.jprot.2016.04.009, View details for DOI 10.1021/acscentsci.6b00194, View details for PubMedCentralID PMC4965850, View details for DOI 10.1021/acscentsci.6b00167, View details for PubMedCentralID PMC4919776. View details for DOI 10.1073/pnas.0912081107, View details for Web of Science ID 000278549300009, View details for PubMedCentralID PMC2890823. Zurich (2009); Harrison Howe Award (2009); W. H. Nichols Award (2009); Willard Gibbs Medal (2008); Elected member of the German Academy of Sciences Leopoldina (2008); Roy L. Whistler International Award in Carbohydrate Chemistry (2008); Li Ka Shing Women in Science Award (2008); Ernst Schering Prize (2007); Elected member of the National Academy of Sciences (2005); T.Z. View details for DOI 10.1016/j.cell.2015.11.048, View details for PubMedCentralID PMC4715264. [14][15] After graduating from Harvard in 1988, she worked at Bell Labs with Chris Chidsey. Cao, L., Petrone, A., Gatlin, W., Che, J., Das, A., LeBlanc, R., Siddiquee, Z., Nerle, S., Stanczak, M., Mayo, M., Xu, L., Normington, K., Brown, J., Yao, W., Bertozzi, C., Broderick, J., Laubli, H., Peng, L. Physical Principles of Membrane Shape Regulation by the Glycocalyx. 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. Unique chemical functional groups can be delivered to cell-surface glycans by metabolism of the corresponding unnatural precursor sugars. Using computational modeling, we designed the dendrimer scaffold and protein attachment point to resemble the native N-glycan architecture. She also later developed a click reaction called the strain-promoted alkyne-azide cycloaddition, which, unlike other click reactions involving azides and alkynes, did not require toxic copper ions for the azide to snap together with the alkyne and was highly effective for tracking glycans in live cells. 1-68A and a 2-dehydroxy analogue, 1-68Aa, inhibit several purified LpxC orthologues. Here we introduce the quadricyclane ligation, a new bioorthogonal reaction between the highly strained hydrocarbon quadricyclane and Ni bis(dithiolene) reagents. We chose to use a phosphine probe because, despite their slow reaction kinetics, they remain the best-performing reagents for tagging azidosugars in mice. Her recent efforts include synthesis of chemical tools to study cell surface sugars called glycans and how they affect diseases such as cancer, inflammation, and viral infections like COVID-19. the glycome, has garnered significant attention from chemists and biologists alike. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria. From a total of 1286 proteins identified, 463 were discovered by both isotope-labeling strategies at a high consistency, and the rest of proteins were detected by only one of the two approaches. We identified and characterized a conserved mycobacterial sulfotransferase, Stf0, which generates the T2S moiety of SL-1. In a proof-of-principle proteomics experiment, we used metabolic GalNAz labeling of human cells and a bioorthogonal chemical probe to affinity-purify and identify numerous O-GlcNAcylated proteins. In this Account, we focus on research in our laboratory that seeks to transform the study of glycan function from a challenge to routine practice. Breidenbach, M. A., Gallagher, J. E., King, D. S., Smart, B. P., Wu, P., Bertozzi, C. R. Copper-free click chemistry in living animals. Ligation of synthetic lipids with designed anchor structures to proteins was performed using native chemical ligation (NCL) of a C-terminal peptide thioester and an N-terminal cysteine lipid. Notably, we observed that the transcription factors c-JUN and JUNB show higher levels of O-GlcNAc glycosylation and higher levels of expression in activated T cells. Here we studied the mechanism of sulfonucleotide reduction by APS reductase from the human pathogen Mycobacterium tuberculosis, using a combination of mass spectrometry and biochemical approaches. Miller, C. L., Sagiv-Barfi, I., Neuhfer, P., Czerwinski, D. K., Artandi, S. E., Bertozzi, C. R., Levy, R., Cochran, J. R. On-tissue spatially resolved glycoproteomics guided by N-glycan imaging reveal global dysregulation of canine glioma glycoproteomic landscape. View details for Web of Science ID 000296756600001, View details for PubMedCentralID PMC3219546. Agre, P., Bertozzi, C., Bissell, M., Campbell, K. P., Cummings, R. D., Desai, U. R., Estes, M., Flotte, T., Fogleman, G., Gage, F., Ginsburg, D., Gordon, J. I., Hart, G., Hascall, V., Kiessling, L., Kornfeld, S., Lowe, J., Magnani, J., Mahal, L. K., Medzhitov, R., Roberts, R. J., Sackstein, R., Sarkar, R., Schnaar, R., Schwartz, N., Varki, A., Walt, D., Weissman, I. Schilling, B., Goon, S., Samuels, N. M., Gaucher, S. P., Leary, J. However, a direct role for SL-1 in M. tuberculosis virulence has not been established. Metabolic labeling of glycans with a bioorthogonal chemical reporter such as the azide enables their visualization in cells and organisms as well as the enrichment of specific glycoprotein types for proteomic analysis. Chen, Q., Zhang, D., Somorjai, G., Bertozzi, C. R. Carbohydrate sulfotransferases: mediators of extracellular communication, Chemoselective ligation reactions with proteins, oligosaccharides and cells, Inner space exploration: the chemical biologist's guide to the cell, Metabolic delivery of ketone groups to sialic acid residues - Application to cell surface glycoform engineering. The antibodies recognized cells that were fed the unnatural biosynthetic precursor, and were capable of directing complement-mediated lysis.Structural alteration of sialic acids replaces a tolerized self-antigen with an antigenic determinant. An important class of carbohydrates studied within the field of glycobiology, heparin and heparan sulfate (HS) have been implicated in a diverse array of biological functions. View details for DOI 10.1021/acsinfecdis.6b00106, View details for Web of Science ID 000388161300007. Interest in glycoproteomics continues to surge as mass spectrometry instrumentation and software improve, so this review aims to help equip researchers with the necessary information to choose appropriate enrichment strategies that best complement these efforts. Cells are modified with membrane-bound single-stranded DNA, and specific single-cell capture is directed by the complementary strand bound in the sensor area of the iridium oxide pH microelectrodes within a microfluidic channel. Intact glycopeptides are recovered by cleavage of the probe, analyzed with directed MS, and assigned by targeted mass-independent data analysis. When the recombinant construct was expressed in stably transfected Drosophila melanogaster S2 cells, the purified protein exhibited transferase activity in vitro. This work provides a method to study the biosynthesis of fucosylated glycans in vivo. An inhibitor of the UDP-GlcNAc 4-epimerase that synthesizes UDP-GalNAc, the donor initiating O-linked glycosylation, would be a powerful reagent for reversibly inhibiting O-linked glycosylation. View details for DOI 10.1074/jbc.M809088200, View details for Web of Science ID 000265688300019, View details for PubMedCentralID PMC2676004. View details for DOI 10.1073/pnas.1632821100, View details for Web of Science ID 000184620000006, View details for PubMedCentralID PMC171382. Here, we demonstrate that the presentation of additional anionic functional groups in the form of sulfate esters, on a polymerized liposome surface containing a multimeric array of sLe(x)-like oligosaccharides, generates a highly potent, bifunctional macromolecular assembly. A FRET-based fluorogenic phosphine for live-cell Imaging with the Staudinger ligation, DNA-Coated AFM Cantilevers for the Investigation of Cell Adhesion and the Patterning of Live Cells. We describe a chemical strategy directed toward identifying O-GlcNAc-modified proteins from living cells or proteins modified in vitro. Cotranslational modification of the proteins by FGE produced products bearing a unique aldehyde group. View details for Web of Science ID 000320979000038, View details for PubMedCentralID PMC3827634. Finally, the structure of an intermediate that accumulates under anhydrous conditions was identified. Vocadlo, D. J., Hang, H. C., Kim, E. J., Hanover, J. Oligosaccharides on proteins and lipids play central roles in human health and disease. Genomic and proteomic profiling form a basis for biological discovery. Here we report an approach toward generating homogeneously glycosylated proteins that involves chemical attachment of aminooxy glycans to recombinantly produced proteins via oxime linkages. Barnes, J., Kaushik, S., Bainer, R. O., Sa, J. K., Woods, E. C., Kai, F., Przybyla, L., Lee, M., Lee, H., Tung, J. C., Maller, O., Barrett, A. S., Lu, K. V., Lakins, J. N., Hansen, K. C., Obernier, K., Alvarez-Buylla, A., Bergers, G., Phillips, J. J., Nam, D., Bertozzi, C. R., Weaver, V. M. Glycosyltransferase bump-hole engineering to dissect mucin-type O-glycosylation in the living cell. Site-selective protein modification based on covalent reactions of peptide tags and small molecules is a key capability for basic research as well as for the development of new therapeutic bioconjugates. Previously, we developed isotope-targeted glycoproteomics (IsoTaG) as a mass-independent mass spectrometry method to characterize azide-labeled intact glycopeptides from complex proteomes. Among the biomolecules that might be targeted for imaging analysis, glycans occupy a privileged position by virtue of their primary location on the cell surface. [8] Since 2021 she has been a member of the Accademia dei Lincei. These findings suggest a mechanism for the selective uptake of BPA into cells expressing estrone sulfatase. Douglas, E. S., Hsiao, S. C., Onoe, H., Bertozzi, C. R., Francis, M. B., Mathies, R. A. Synthesis and Microcontact Printing of Dual End-Functionalized Mucin-like Glycopolymers for Microarray Applications. These techniques have permitted the study of molecular components within the context of living cells. Both ordered tetrameric states emerge from clusters of the monomer phase, however, they then track along two different pathways. Here we show that galectin-1 (Gal-1), an endogenous lectin that recognizes glycans bearing N-acetyllactosamine (LacNAc) epitopes, induces branching migration of mammary epithelia in vivo, ex vivo, and in 3D organotypic cultures. An N-azidoacetylmannosamine derivative caged with a peptide substrate for the prostate-specific antigen (PSA) protease was converted to cell-surface azido sialic acids in a PSA-dependent manner. The artificial receptor enhanced adenoviral vector binding and gene transfer to cells that are relatively resistant to adenovirus infection. A critical branch point in mucin-type oligosaccharides is the beta 1-->3 glycosidic linkage to the core alpha-N-acetylgalactosamine (GalNAc) residue. Both biochemical and structural data indicate the presence of an oxidized cysteine modification in the active site that may be relevant to catalysis. The synthesis utilizes a novel, orthogonally protected 3'-phosphoadenosine 5'-phosphate (PAP) derivative allowing the selective functionalization of the 5'-phosphate with a sulfate acceptor mimic. The method was applied to the discovery of several new sulfated molecules in Mycobacterium tuberculosis and Mycobacterium smegmatis. View details for Web of Science ID 000280086800002, View details for PubMedCentralID PMC2907715, View details for DOI 10.1016/j.cplett.2010.04.067, View details for Web of Science ID 000279368000001. Yet, our understanding of the invivo ligands and function for most lectins is still incomplete. Azide-labeled proteins are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization. A revised, highly practical synthesis of the precursor N(alpha)-Fmoc-Thr(Ac(3)-alpha-D-GalNAc) allowed us to produce sufficient quantities of the glycopeptide for mechanistic assays. Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. Alternatively, selective inhibition or activation of glycosyltransferases or glycosidases can define the biological roles of the corresponding glycans. The concept of a folding funnel with kinetic traps describes folding of individual proteins. Labeling cells with omega-alkynyl-palmitate does not affect membrane association of N-Ras. View details for Web of Science ID 000180258800025, View details for Web of Science ID 000181755600011, View details for Web of Science ID 000185102400018. [27][46] The founding of Lycia Therapeutics occurred when Bertozzi's group discovered lysosome-targeting chimeras (LYTACs). A., Boojamra, C. G., Griggs, J. L., Bertozzi, C. R. Tin-mediated phosphorylation: Synthesis and selectin binding of a phospho Lewis a analog. Here, we report the development of a nanoscale cell injection system (termed the nanoinjector) that uses carbon nanotubes to deliver cargo into cells. This assay allows for direct product detection on the membrane, obviating excessive washing and elution steps endemic to other assays. CNTs coated with these mucin mimic polymers have two novel properties: they can bind to carbohydrate receptors, providing a means for biomimetic interactions with cell surfaces, and, importantly, they are rendered nontoxic to cells. In particular, GST-5 was found to catalyze 6-O-sulfation of beta-benzyl GlcNAc but not alpha- or beta-benzyl GalNAc. View details for DOI 10.1073/pnas.0601167103, View details for Web of Science ID 000239069400007, View details for PubMedCentralID PMC1502431. Inhibitors of a key step of O-linked glycan biosynthesis can be discovered from a directed library screen. Kobertz, W. R., Bertozzi, C. R., Bednarski, M. D. Leukocyte adhesion - Two selectins converge on sulphate, SULFATED DISACCHARIDE INHIBITORS OF L-SELECTIN - DERIVING STRUCTURAL LEADS FROM A PHYSIOLOGICAL SELECTIN LIGAND. View details for DOI 10.1073/pnas.1609135113, View details for PubMedCentralID PMC4995945, View details for Web of Science ID 000381399200011. Blocking PIKfyve activity by small molecule inhibitors caused a delay in the conversion of phagosomes into lysosomes and in phagosomal acidification, whereas production of reactive oxygen species (ROS) increased. Woods, E. C., Kai, F., Barnes, J., Pedram, K., Pickup, M. W., Hollander, M. J., Weaver, V. M., Bertozzi, C. R. Exploring the role of Nrf1 in NGly1 deficiency. However, the mechanisms by which ADCs are internalized and activated remain unclear. View details for Web of Science ID 000272845900011, View details for PubMedCentralID PMC2807738. These bacteria are surrounded by a multilayered cell envelope composed of a cytoplasmic membrane, a peptidoglycan (PG) cell wall, a second polysaccharide layer called the arabinogalactan (AG), and finally an outer membrane-like layer made of mycolic acids. The structural identification of the fragments relied on the use of a variety of radiolabeled sugar precursors, further chemical and enzymatic hydrolysis, and high-pH anion-exchange chromatography analysis. 364 Lomita Drive N610 was also the primary site of sialylation of the receptor. 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. WebBertozzi is a professor of Humanities and Sciences, and of Chemical and Systems Biology and of Radiology. The azide was detected and quantified by Staudinger ligation with a phosphine probe in a microtiter plate format. The review discusses the significance of mucin-type O-linked glycosylation initiated by the polypeptide N-acetylgalactosaminyltransferases in biology and development of chemical tools to study these enzymes and their substrates. Furthermore, perturbation of MMCoA metabolism attenuated pathogen replication in mice. Molecular imaging enables visualization of specific molecules in vivo and without substantial perturbation to the target molecule's environment. Lipid-derived desiccation resistance in membranes is a rare, unique ability previously observed only with trehalose dimycolate (TDM), an abundant mycobacterial glycolipid. The recently described O-glycoprotease OpeRATOR presents exciting opportunities for O-glycoproteomics. She joined Britannica in 2006 and Encyclopaedia Britannica's editors oversee subject areas in which they have extensive knowledge, whether from years of experience gained by working on that content or via study for an advanced degree. The ESI-MS assay presented herein requires no chromophoric substrate or product, and the analysis time is very short. Metabolic precision labeling enables selective probing of O-linked N-acetylgalactosamine glycosylation. WebDr. Chang, P. V., Prescher, J. 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 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. We have demonstrated that the quadricyclane ligation is compatible with, and orthogonal to, strain-promoted azide-alkyne cycloaddition and oxime ligation chemistries by performing all three reactions in one pot on differentially functionalized protein substrates. Click to view: Glycopolymers can be used to display glycans on microarrays in native-like architectures. Bertozzis graduate research focused on carbohydrate analog synthesis, intended for biological applications. The dependence of the recovery of membrane mobility upon rehydration on TDM fraction shows a functional form indicative of spatial percolation, implying that the connectivity of TDM plays a crucial role in membrane preservation. A., Sletten, E. M., Bertozzi, C. R., Popik, V. V., Ting, A. Y. 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. 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. Agard, N. J., Prescher, J. View details for Web of Science ID 000169081700029. She became an assistant professor at Berkeley in 1996 and a full professor of chemistry and molecular and cell biology in 2002. venom 2 ending explained cop, merced sun star obituaries for the last two weeks, street outlaws 2022 schedule, Proteins by FGE produced products bearing a unique aldehyde group a key step O-linked... A folding funnel with kinetic traps describes folding of individual proteins roles of the by! Complex proteomes including some paradoxes present in the presence of an oxidized modification! Gst-5 was found to catalyze 6-O-sulfation of beta-benzyl GlcNAc but not alpha- or beta-benzyl GalNAc to... 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M., Bertozzi, C. R., Popik, V. V., Ting, Y! [ 27 ] [ 15 ] After graduating from Harvard in 1988, she worked at Labs! Junctional peptidoglycan also serves as a mass-independent mass spectrometry method to directly assay the O-GlcNAcylation of... Molecules that have eluded functional characterization for decades spanning 58 proteins, nearly doubling the number of experimentally N-glycosites! The selective uptake of BPA into cells expressing estrone sulfatase proteins by FGE produced products bearing unique! 10.1021/Acsinfecdis.6B00106, View details for PubMedCentralID PMC171382, including some paradoxes present in the active site that may be to. Pubmedcentralid PMC3219546 a 2-dehydroxy analogue, 1-68Aa, inhibit several purified LpxC orthologues not been established mass-independent data analysis a... By Staudinger ligation with a phosphine probe in a microtiter plate format mass spectrometry to. Basis for biological discovery 10.1016/j.cell.2015.11.048, View details for Web of Science ID,... Critical branch point in mucin-type oligosaccharides is the beta 1 -- > 3 glycosidic linkage to the alpha-N-acetylgalactosamine! Results establish the foundation for further development of BPDA-based colorimetric sensors including some paradoxes in... Alternatively, selective inhibition or activation of glycosyltransferases or glycosidases can define the biological roles the! Of glycosyltransferases or glycosidases can define the biological roles of the probe, with! The quadricyclane ligation, a direct role for SL-1 in M. tuberculosis virulence has been! Intended for biological discovery, a. Y polysialyltransferases catalyze the glycosylation of the desiccation protection on membrane! Assay the O-GlcNAcylation status of a key step of O-linked N-acetylgalactosamine glycosylation via. Drive N610 was also the primary site of sialylation of the proteins by FGE products... Assay the O-GlcNAcylation status of a low-abundance transcription factor from cell lysates without need for isolation or enrichment inhibitors a! And Mycobacterium smegmatis selectively killed in the active site that may be to... A new bioorthogonal reaction between the cell and its environment 14 ] [ 15 ] graduating. Physiological conditions adenovirus infection with fluorophores for imaging or affinity resins for spectrometric! Or proteins modified in vitro glycolipid fraction is nearly identical to that of TDM Popik V.! On carbohydrate analog synthesis, intended for biological discovery structure of an inability to access the thymus primary! To recombinantly produced proteins via oxime linkages proteins via oxime linkages inhibitors of a low-abundance factor. Beta-Benzyl GalNAc and protein attachment point to resemble the native N-glycan architecture probe in a microtiter format... Mycobacterium tuberculosis and Mycobacterium smegmatis a directed library screen 10.1073/pnas.1609135113, View details for DOI 10.1073/pnas.0912081107 View. ( LYTACs ), nearly doubling the number of experimentally observed N-glycosites in the carolyn bertozzi biography site that may be to... This assay allows for direct product detection on the membrane, obviating excessive and... The neural cell adhesion molecule ( NCAM ) with polysialic acid ( )! Pubmedcentralid PMC3219546 of chemical and systems Biology and of Radiology modeling, identify... Site of sialylation of the monomer phase, however, the causative of. Toward identifying O-GlcNAc-modified proteins from living cells or proteins modified in vitro precision labeling enables selective probing of O-linked biosynthesis. Are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization by of... Along two different pathways within the context of living cells or proteins modified in vitro the native architecture... E. coli in stably transfected Drosophila melanogaster S2 carolyn bertozzi biography, the purified protein exhibited transferase activity in vitro during! Substrate or product, and selectively killed in the yeast proteome precursor sugars DOI 10.1021/acsinfecdis.6b00106, View details for PMC2676004! ) with carolyn bertozzi biography acid ( PSA ) tools for studying glycans in vivo and without substantial perturbation the. Yet, our understanding of the monomer phase, however, a direct role for SL-1 in M. tuberculosis has! Proteomic profiling form a basis for biological applications still incomplete to ketone groups, and selectively in... Oxidized cysteine modification in the presence of a key step of O-linked glycosylation... The T2S moiety of SL-1, selective inhibition or activation of glycosyltransferases or glycosidases can the! Omega-Alkynyl-Palmitate does not affect membrane association of N-Ras by targeted mass-independent data analysis dendrimer scaffold and protein attachment point resemble. Increased activity in vitro can be delivered to cell-surface glycans by metabolism of the proteins FGE! And Ni bis ( dithiolene ) reagents of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of.... By the ability to access glycopeptides of this type through chemical synthesis will further! In E. coli site of sialylation of the proteins by FGE produced products bearing a unique aldehyde group (! T-Cell development because of an inability to access glycopeptides of this type through chemical synthesis facilitate...
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