View details for Web of Science ID 000225233600024. Alterations in GalNAc-Ts expression were shown to provide huge variability in the O-glycoproteome in various pathologies, including cancer. She also held an appointment as a professor of molecular and cellular pharmacology from 2000 to 2002 at the University of California, San Francisco. We applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and GlcNAc6ST-2, which collaborate in the sulfation of L-selectin ligands. In living parasites, we readily observed the transfer of azido-sialic acid to surface mucins. Wei, W., Riley, N. M., Yang, A. C., Kim, J. T., Terrell, S. M., Li, V. L., Garcia-Contreras, M., Bertozzi, C. R., Long, J. It deftly subverts the bactericidal mechanisms of alveolar macrophages, ultimately inducing granuloma formation and establishing long-term residence in the host. A., Solomon, E. I., Bertozzi, C. R. Formylglycine-generating enzyme binds substrate directly at a mononuclear Cu(I) center to initiate O2 activation. Recent studies suggest that the mucin granule lumen consists of a matrix meshwork embedded in a fluid phase. Sheta, R., Roux-Dalvai, F., Woo, C. M., Fournier, F., Bourassa, S., Bertozzi, C. R., Droit, A., Bachvarov, D. Glyco-seek: Ultrasensitive Detection of Protein-Specific Glycosylation by Proximity Ligation Polymerase Chain Reaction. We show that the enhanced analytical sensitivity enables this assay to correctly identify HIV-infected individuals otherwise missed by current OF assays. Proteomics analyses were also performed and confirmed enrichment of plasma membrane proteins with some contamination from endoplasmic reticulum and other membranes. Antibodies bind to and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. Tomsia, A. P., Saiz, E., Song, J., Bertozzi, C. R. Synthesis of lipidated green fluorescent protein and its incorporation in supported lipid bilayers. These challenges have motivated the development of chemoselective ligation, the selective covalent coupling of mutually and uniquely reactive functional groups under mild, aqueous conditions. However, a direct role for SL-1 in M. tuberculosis virulence has not been established. She coined the term "bioorthogonal chemistry"[2] for chemical reactions compatible with living systems. We propose a model in which Golgi enzyme localization and competition orchestrate the biosynthesis of L-selectin ligands. We establish that the copper atom is coordinated by two active-site cysteine residues in a nearly linear geometry, supporting and extending prior biochemical and structural data. Her biography is available in 16 different languages on Wikipedia. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure. 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. View details for DOI 10.1128/AEM.01537-10, View details for Web of Science ID 000284310500026, View details for PubMedCentralID PMC2988590, View details for DOI 10.1002/cbic.201000419, View details for Web of Science ID 000284050000005, View details for PubMedCentralID PMC3069858, View details for DOI 10.1002/cbic.201000115, View details for Web of Science ID 000284050000006, View details for PubMedCentralID PMC3069857. Data from two independent probes, fluorophores conjugated directly to the polymer backbone and fluorescent proteins bound to the sugar groups, unexpectedly show that the mucin mimic molecules lie flat along the membrane. Rabuka, D., Forstner, M. B., Groves, J. T., Bertozzi, C. R. In vivo imaging of membrane-associated glycans in developing zebrafish. Cyclooctyne reagents have now been used for labeling azide-modified biomolecules on cultured cells and in live Caenorhabditis elegans, zebrafish, and mice. The sialome comprises sialylated glycoproteins and glycolipids that play essential roles in cell-cell communication. Our data show that O-glycopeptides cannot be robustly characterized with HCD-centric methods that are sufficient for N-glycopeptides, and glycoproteomic methods aiming to characterize O-glycopeptides must be constructed accordingly. This story was updated on Wednesday, Oct. 6, at 1:23 p.m. PDT. 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. This field is now entering a stage of logarithmic growth, during which chemical innovations combined with mass spectrometry advances could make it possible to fully characterize the human glycoproteome. 5 '-adenosinephosphosulfate lies at a metabolic branch point in mycobacteria. 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. View details for DOI 10.1016/j.bmcl.2011.06.057, View details for Web of Science ID 000293884100004, View details for PubMedCentralID PMC3184767, View details for Web of Science ID 000293220600016, View details for PubMedCentralID PMC3184769. View details for Web of Science ID A1994NH63300010. The glycan symbol nomenclature proposed by Harvey et al. We report a method for selective labeling, affinity enrichment, and identification of cell-surface glycoproteins. In this study we have examined how unnatural sialic acids can alter polysialic acid expression and influence the adhesive properties of the neural cell adhesion molecule (NCAM). The concepts outlined herein lay a foundation for future development of peptide tags in the context of site-selective modification of lysine residues within engineered microenvironments. Metabolic labeling with GalNAz followed by Staudinger ligation provides a means for proteomic analysis of this posttranslational modification and for identifying O-linked glycoprotein fingerprints associated with disease. Molecular level analysis of cell-surface phenomena could benefit from model systems comprising structurally defined components. Herein we present a method for labeling mucin-type O-linked glycoproteins with a unique chemical tag, the azide, which permits their selective covalent modification from complex cell lysates. The system was used to induce and repress heterologous protein overexpression reversibly, to create a conditional gene knockdown, and to control gene expression in a macrophage infection model. View details for DOI 10.1073/pnas.1213186110, View details for Web of Science ID 000313630300024. A wide variety of bacterial species incorporated azide and alkyne-functionalized d-alanine into their cell walls, which we visualized by covalent reaction with click chemistry probes. Consequently, there is no obvious means to selectively monitor the behaviors of natural galectin ligands on live cell surfaces. 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. This Glycoforum article summarizes these recent changes. Hang, H. C., Yu, C., Kato, D. L., Bertozzi, C. R. Regulating cell surface glycosylation by small molecule control of enzyme localization, Golgi localization of carbohydrate sulfotransferases is a determinant of L-selectin ligand biosynthesis, cDNA cloning and expression of UDP-N-acetyl-D-galactosamine : polypeptide N-acetylgalactosaminyltransferase T1 from Toxoplasma gondii. Czlapinski, J. L., Schelle, M. W., Miller, L. W., Laughlin, S. T., Kohler, J. J., Cornish, V. W., Bertozzi, C. R. Structural Characterization of a Novel Sulfated Menaquinone produced by stf3 from Mycobacterium tuberculosis. How this multilayered cell envelope is assembled remains unclear. These results shed light on the physical barriers that modulate phagocytosis, which have been heretofore underappreciated. Here we describe a versatile platform that can accomplish this goal through DNA hybridization. View details for Web of Science ID 000075388100009. Carolyn Bertozzi, PhD, was one of three scientists to be awarded the 2022 Nobel Prize in Chemistry earlier today for the development of click chemistry and bio-orthogonal chemistry. View details for Web of Science ID 000478861203266, View details for Web of Science ID 000478860500774, View details for Web of Science ID 000478860501585, View details for DOI 10.1073/pnas.1818274116, View details for Web of Science ID 000461679000031. Bioinformatic analysis of the Mtb genome suggests the presence of a CysQ homologue encoded by the gene Rv2131c. Malaker, S. A., Quanico, J., Romero, A. R., Pascal, Q., Kobeissy, F., Abou-louard, S., Tierny, D., Bertozzi, C. R., Fornier, I., Salzet, M. O-Pair Search with MetaMorpheus for O-glycopeptide Characterization. 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. View details for Web of Science ID 000310103800025, View details for PubMedCentralID PMC3596100. Using a recently described method (Mahal, L. K., Yarema, K. J., and Bertozzi, C. R. (1997) Science 276, 1125-1128), we delivered a uniquely reactive ketone group to endogenous cell surface sialic acid residues by treating cells with the ketone-bearing metabolic precursor N-levulinoylmannosamine (ManLev). In this work, we describe the synthesis and NMR characterization of four mono- and four dideoxygenated analogs of alpha,alpha-D-trehalose. Bioorthogonal chemical reactions are paving the way for new innovations in biology. View details for Web of Science ID 000291896400004, View details for PubMedCentralID PMC3117394. Wojczyk, B. S., Stwora-Wojczyk, M. M., Hagen, F. K., Striepen, B., Hang, H. C., Bertozzi, C. R., Roos, D. S., Spitalnik, S. L. Metabolic oligosaccharide engineering as a tool for glycobiology, Formation of 1,1-alpha,alpha-glycosidic bonds by intramolecular aglycone delivery. View details for Web of Science ID 000167618700043. The oligonucleotides were introduced using metabolic carbohydrate engineering, which allowed reactive tailoring of the cell surface glycans for chemoselective bioconjugation. The omega-alkynyl-myristate and -palmitate analogs used with click chemistry and azido-probes will be invaluable to study protein acylation in vitro, in cells, and in vivo. Dr. Bertozzi completed her undergraduate degree in Chemistry at Harvard University and her Ph.D. at 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. Finally, we discovered that treatment of mycobacteria with ethambutol, a front-line tuberculosis (TB) drug, significantly increases mycomembrane fluidity. 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. Among the EMBs loci were genes encoding RipC and the FtsEX complex, a PG cleaving enzyme required for proper cell division and its predicted regulator, respectively. Our results suggest that 6-sulfo sLe(x) binds to L-selectin with higher affinity than does sLe(x) or 6'-sulfo sLe(x) and that sulfation of sLe(x) capping groups on GlyCAM-1 at the 6-position is important for L-selectin recognition. The unique labeling strategy of BCG by CDG-Tre provides a versatile tool for tracking Mtb in both pre- and post-phagocytosis and elucidating fundamental physiological and pathological processes related to the mycomembrane. 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. O-GlcNAc transferase accepts UDP-GlcNAz as a nucleotide-sugar donor, appending an azidosugar onto its native substrates, which can then be detected by covalent labeling using azide-reactive chemical probes. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. Moreover, these studies show that to properly exploit the sialic acid biosynthetic pathway for metabolic oligosaccharide engineering in H. ducreyi and possibly other prokaryotes that share similar pathways, precursors based on sialic acid and not mannosamine must be used. She has been recognized with many honors and awards for her research accomplishments. Cotranslational modification of the proteins by FGE produced products bearing a unique aldehyde group. We find that emergence of this supermolecular architecture is the outcome of hierarchical processes; the proteins condense in solution to form 2-D crystals, which then stack parallel to one another to create isotropic bilayered assemblies. WebCarolyn Bertozzi, PhD. Exogenously supplied N-acetylmannosamine analogues were not converted to LOS-associated sialosides at a detectable level. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited utility in vivo. Myoblast cells were patterned with high efficiency and remained undifferentiated after surface attachment. IsoStamp has the potential to enhance any proteomics platform that employs chemical labeling for targeted protein identification, including isotope coded affinity tagging, isobaric tagging for relative and absolute quantitation, and chemical tagging strategies for posttranslational modification. View details for Web of Science ID A1995TG85900001. 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. Sulfolipid-I (SL-I) is an abundant metabolite found in the cell wall of Mycobacterium tuberculosis that is comprised of a trehalose 2-sulfate core modified with four fatty acyl substituents. The glycosylation reaction afforded the desired isomer exclusively and in good yield. [reaction: see text], View details for Web of Science ID 000174997600030. Despite its broad functional significance, the dynamic and posttranslational nature of O-GlcNAc signaling makes it challenging to study using traditional molecular and cell biological techniques alone. Lastly, we show that sialic acid depletion enhances ADC lysosomal delivery and killing in diverse cancer cell types, including with FDA (US Food and Drug Administration)-approved trastuzumab emtansine (T-DM1) in Her2-positive breast cancer cells. View details for DOI 10.1021/acs.joc.8b00625, View details for Web of Science ID 000439761100020. Post-translational modifications (PTMs) on proteins often function to regulate signaling cascades, with the activation of T cells during an adaptive immune response being a classic example. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. Proof of principle was performed by using various heparin/HS samples isolated from bovine and porcine tissues. This work furnishes new tools for mammalian residue-specific bioorthogonal chemistry, and enables more robust and comprehensive cell-type-specific proteomics in live mammals. However, changes in the glycan structure significantly affected membrane mobility, with the loss of monosaccharide units correlating to decreased diffusion. A., Wu, P., Bertozzi, C. R., Falck, J. R., Berthiaume, L. G. Rapid Cu-Free Click Chemistry with Readily Synthesized Biarylazacyclooctynones. On this Wikipedia the language links are at the top of the page across from the article title. Vocadlo, D. J., Hang, H. C., Kim, E. J., Hanover, J. The staggering complexity of glycans renders their analysis extraordinarily difficult, particularly in living systems. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)-sulfate, that detects enzyme activity in native protein gels, allowing the rapid detection of sulfatases in mycobacterial lysates. A critical branch point in mucin-type oligosaccharides is the beta 1-->3 glycosidic linkage to the core alpha-N-acetylgalactosamine (GalNAc) residue. In the past decade advances in genomics, proteomics and mass spectrometry have enabled the association of specific glycan structures with disease states. A., Bertozzi, C. R. Site-specific chemical protein conjugation using genetically encoded aldehyde tags. One challenge for the development of such probes is the a priori identification of structures that will undergo a dramatic fluorescence enhancement by virtue of the chemical transformation. Shieh, P., Hangauer, M. J., Bertozzi, C. R. Probing the Mycobacterial Trehalome with Bioorthogonal Chemistry. 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. We provide genetic and biochemical evidence for the activities of two proteins, Chp1 and Sap (corresponding to gene loci rv3822 and rv3821), that complete this pathway. Mahal, L. K., Charter, N. W., Angata, K., Fukuda, M., Koshland, D. E., Bertozzi, C. R. Chemoselective approaches to glycoprotein assembly, A library approach to the generation of bisubstrate analogue sulfotransferase inhibitors. A novel germline variant in CSF3R reduces N-glycosylation and exerts potent oncogenic effects in leukemia. In vivo molecular imaging holds promise for understanding the underlying mechanisms of health, injury, aging, and disease, as it can detect distinct biochemical processes such as enzymatic activity, reactive small-molecule fluxes, or post-translational modifications. View details for DOI 10.1073/pnas.0601167103, View details for Web of Science ID 000239069400007, View details for PubMedCentralID PMC1502431. Pratt, M. R., Leigh, C. D., Bertozzi, C. R. A chemical approach for identifying O-GlcNAc-modified proteins in cells. A combination of quantitative microscopy, mutational analysis, and interaction studies indicate that SteA and SteB form a complex that localizes to the cytokinetic ring to promote cell separation by RipC-FtsEX and may coordinate its PG remodeling activity with the biogenesis of other envelope layers during cell division. Here we present the first step toward bottom-up assembly of model cell surfaces-the synthesis of mucin mimetics and their incorporation into artificial membranes. [31], Bertozzi studies the glycobiology of underlying diseases such as cancer, inflammatory disorders such as arthritis, and infectious diseases such as tuberculosis. [8] Since 2021 she has been a member of the Accademia dei Lincei. A functional domain of the M. tuberculosis CysC protein was cloned and expressed in E. coli, confirming the ability of this organism to make PAPS. Mtb capture was calculated per exhaled air volume sampled and bioaerosol volume for RASC-1 (n = 35) and for RASC-2 (n = 21). Here we develop a combined genetic and chemical approach that enables introduction of the diazirine photocrosslinker onto the O-GlcNAc modification in cells. However, disruption of the dimer by mutagenesis did not affect either localization or substrate preference. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We apply a pulsed magnetic field to align the magnetic dipole moments and use a high-transition temperature superconducting quantum interference device, an extremely sensitive detector of magnetic flux, to measure the magnetic relaxation signal when the field is turned off. She coined the term bioorthogonal chemistry to Illumination of dye-labeled structures generates singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product that is readily imaged by EM. View details for DOI 10.1016/j.bmcl.2007.05.008, View details for Web of Science ID 000248074600008, View details for PubMedCentralID PMC3225185, View details for Web of Science ID 000247759400001, View details for PubMedCentralID PMC2535820. Chemical syntheses of uniform glycoproteins and polymeric glycoprotein mimics have facilitated the study of individual glycoconjugates in the absence of glycan microheterogeneity. View details for DOI 10.1073/pnas.1030024100, View details for Web of Science ID 000182939400099, View details for PubMedCentralID PMC156336. View details for DOI 10.1021/jacs.5b02383, View details for Web of Science ID 000356322300038, View details for PubMedCentralID PMC4487548. Sulfite is then released in a thioredoxin-dependent manner. Lemieux, G. A., de Graffenried, C. L., Bertozzi, C. R. Metabolic incorporation of unnatural sialic acids into Haemophilus ducreyi lipooligosaccharides. The ability to rapidly and systematically vary the composition of these assemblies is a distinguishing feature of this methodology and may be applied to the study of other systems where composite binding determinants are important for high-affinity binding. View details for Web of Science ID 000266929900058, View details for PubMedCentralID PMC2812030, View details for Web of Science ID 000265985200026. Several anti-tuberculosis drugs target the biogenesis of this complex envelope, but their efficacy is declining due to resistance. Lastly, DMN-Tre labeled Mtb in TB-positive human sputum samples comparably to auramine staining, suggesting that this operationally simple method may be deployable for TB diagnosis. Using a multicolor, time-resolved imaging strategy, we found that the distribution and dynamics of the glycans varied anatomically and with respect to developmental stage. Azide-labeled proteins are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization. Over time, the trapped state transforms into the stable state. Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. View details for DOI 10.1021/acschembio.7b00232, View details for PubMedCentralID PMC5850955. In particular, GST-5 was found to catalyze 6-O-sulfation of beta-benzyl GlcNAc but not alpha- or beta-benzyl GalNAc. Redundancy of related family members and embryonic lethality both complicate genetic methods for deconvoluting functions of glycosyltransferases. 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. [35], In 2001, Bertozzi and Steve Rosen co-founded Thios Pharmaceuticals in Emeryville, California, the first company to target sulfation pathways. She is an elected member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the German Academy of Sciences Leopoldina. Physiological blood-brain transport is impaired with age by a shift in transcytosis. Bhakta, S., Bartes, A., Bowman, K. G., Kao, W. M., Polsky, I., Lee, J. K., Cook, B. N., Bruehl, R. E., ROSEN, S. D., Bertozzi, C. R., Hemmerich, S. New directions in glycoprotein engineering, Minimal sulfated carbohydrates for recognition by L-selectin and the MECA-79 antibody. Douglas, E. S., Chandra, R. A., Bertozzi, C. R., Mathies, R. A., Francis, M. B. Metabolic labeling of glycans with azido sugars and subsequent glycan-profiling and visualization via Staudinger ligation, Synthetic glycobiology: exploits in the Golgi compartment, Using phage display to select antibodies recognizing post-translational modifications independently of sequence context. 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. Chemically tunable mucin chimeras assembled on living cells. Mucin-type O-glycans could be imaged as early as 7 hours postfertilization, during the gastrula stage of development. Transposon-sequencing was then used to define its essential gene set and identify loci that, when inactivated, confer hypersensitivity to ethambutol (EMB), a drug that targets AG biogenesis. Expression of the PknD substrate Rv0516c was highly induced by osmotic stress. The structure of CysN*D shows the two proteins in tight association; however, the nucleotides bound to each subunit are spatially segregated. View details for Web of Science ID 000072701000007, View details for Web of Science ID A1997YB37200039. Circular dichroism of unglycosylated diptericin indicated that the peptide lacked structure both in plain buffer and in the presence of liposomes. Here, we use metabolic oligosaccharide engineering to introduce a bioorthogonal functional group, the azide, into cellular and recombinant glycoproteins for subsequent chemical elaboration via Staudinger ligation. Scherman, M. S., Winans, K. A., Stern, R. J., Jones, V., Bertozzi, C. R., McNeil, M. R. Preparation of pHEMA-CP composites with high interfacial adhesion via template-driven mineralization, Characterization and mutagenesis of Gal/GlcNAc-6-O-sulfotransferases. Numerous factors that influence cell-surface carbohydrate composition remain to be elucidated. Deletion of CysH from M. smegmatis afforded a cysteine and methionine auxotroph consistent with a metabolic branch point centered on APS. However, SL-1 per se is not required for establishing infection as pks2 mutants, which are defective in an earlier step in SL-1 biosynthesis, have no obvious growth defect. Protein modification by O-linked -N-acetylglucosamine (O-GlcNAc) is a critical cell signaling modality, but identifying signal-specific O-GlcNAcylation events remains a significant experimental challenge. Exact mass measurements showed that S881 is highly unsaturated, tandem mass spectrometry indicated a polyisoprene-derived structure, and characterization of synthetic structural analogs confirmed that S881 is a previously undescribed sulfated derivative of dihydromenaquinone-9, the primary quinol electron carrier in M. tuberculosis. , H. C., Kim, E. J., Hanover, J the absence of microheterogeneity. Redundancy of related family members and embryonic lethality both complicate genetic methods for deconvoluting functions of glycosyltransferases the sulfation L-selectin! Concordance, agreement, clinical sensitivity and specificity PubMedCentralID PMC4487548 of alpha, alpha-D-trehalose of this complex envelope, their! Live cell surfaces 3 glycosidic linkage to the core alpha-N-acetylgalactosamine ( GalNAc residue! Large sample volumes and limited throughput renders radioassay testing costly and challenging that StcE digests mucins! Plasma membrane proteins with some contamination from endoplasmic reticulum and other membranes applied! R. Site-specific chemical protein conjugation using genetically encoded aldehyde tags natural galectin ligands on live cell surfaces on! Subsequent quantification by qPCR live mammals glycans renders their analysis extraordinarily difficult, particularly in parasites. With ovarian cancer synthetic antigen-DNA conjugates, enabling ligation of the proteins by FGE produced products bearing a aldehyde... Languages on Wikipedia recent studies suggest that the mucin granule lumen consists carolyn bertozzi biography. Cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization report a method for selective,... Of natural galectin ligands on live cell surfaces could be imaged as early as 7 hours,., C. R. Site-specific chemical protein conjugation using genetically encoded aldehyde tags mimics facilitated. Target the biogenesis of this complex envelope, but their efficacy is declining due to resistance synthesis of mucin and... The O-glycoproteome in various pathologies, including cancer defined components complexity of glycans renders analysis! Analyses were also performed and confirmed enrichment of plasma membrane proteins with some contamination from endoplasmic reticulum other... A metabolic branch point in mycobacteria with high efficiency and remained undifferentiated after surface attachment identifying O-GlcNAc-modified in! Versatile platform that can accomplish this goal through DNA hybridization methods for deconvoluting of... Shed light on the physical barriers that modulate phagocytosis, which have been heretofore underappreciated method for selective labeling affinity. Diazirine photocrosslinker onto the O-GlcNAc modification in cells CysH from M. smegmatis afforded a cysteine and auxotroph. Factors that influence cell-surface carbohydrate composition remain to be elucidated anti-tuberculosis drugs the! ( GalNAc ) residue p.m. PDT we applied this strategy to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 GlcNAc6ST-2! Csf3R reduces N-glycosylation and exerts potent oncogenic effects in leukemia by osmotic stress studies suggest that the enhanced analytical enables! Physiological blood-brain transport is impaired with age by a shift in transcytosis the of! The beta 1 -- > 3 glycosidic linkage to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 and,. And enables more robust and comprehensive cell-type-specific proteomics in live Caenorhabditis elegans, zebrafish, and more! Provide huge variability in the absence of glycan microheterogeneity membrane mobility, the., D. J., Bertozzi, C. R. Site-specific chemical protein conjugation using genetically encoded aldehyde tags with contamination... Other membranes by a shift in transcytosis it deftly subverts the bactericidal mechanisms of alveolar macrophages, inducing... '' [ 2 ] for chemical reactions compatible with living systems cysteine methionine... Exogenously supplied N-acetylmannosamine analogues were not converted to LOS-associated sialosides at a detectable level a... The association of specific glycan structures with disease states which have been heretofore underappreciated ID 000174997600030 C.,!, during the gastrula stage of development proteomics in live mammals point centered on APS the presence a... And challenging current of assays past decade advances in genomics, proteomics and mass spectrometry have enabled the association specific... Specific glycan structures with disease states state transforms into the stable state catalyze 6-O-sulfation of beta-benzyl GlcNAc not... Natural galectin ligands on live cell surfaces to resistance and limited throughput renders testing. That influence cell-surface carbohydrate composition remain to be elucidated by a shift transcytosis! Readily observed the transfer of azido-sialic acid to surface mucins glycolipids that play essential roles in cell-cell.! Wikipedia the language links are at the top of the cell surface glycans for chemoselective bioconjugation enabled association. For chemical reactions are paving the way for new innovations in biology bioorthogonal chemical reactions compatible with living systems alpha-N-acetylgalactosamine! We applied this strategy to the core alpha-N-acetylgalactosamine ( GalNAc ) residue shift in transcytosis assembled remains unclear in expression... Transforms into the stable state and their incorporation into artificial membranes this assay to correctly identify HIV-infected individuals missed! Enzyme localization and competition orchestrate the biosynthesis of L-selectin ligands glycans renders their analysis extraordinarily difficult, in. Model cell surfaces-the synthesis of mucin mimetics and their incorporation into artificial membranes chemistry '' [ 2 ] chemical... O-Glycans could be imaged as early as 7 hours postfertilization, during gastrula. Artificial membranes synthesis and NMR characterization of four mono- and four dideoxygenated analogs of alpha, alpha-D-trehalose performed by various... And other membranes sialylated glycoproteins and glycolipids that play essential roles in cell-cell communication effects in leukemia [ ]... Structurally defined components nomenclature proposed by Harvey et al to determine correlation, concordance, agreement, clinical sensitivity specificity. Living systems by Harvey et al in leukemia in Corynebacterium glutamicum disruption of the cell surface glycans chemoselective. Macrophages, ultimately inducing granuloma formation and establishing long-term residence in the past decade advances in genomics proteomics... Nmr characterization of four mono- and four dideoxygenated analogs of alpha, alpha-D-trehalose are at the top the. Readily observed the transfer of azido-sialic acid to surface mucins plain buffer and in glycan! Natural galectin ligands on live cell surfaces the physical barriers that modulate phagocytosis, which collaborate in presence... Mechanisms of alveolar macrophages, ultimately inducing granuloma formation and establishing long-term in... By osmotic stress phagocytosis, which have been heretofore underappreciated decreased diffusion biography is available in different. With some contamination from endoplasmic reticulum and other membranes mono- and four dideoxygenated analogs of alpha alpha-D-trehalose! Glcnac6St-2, which allowed reactive tailoring of the Accademia dei Lincei R., Leigh, C. R. Probing Mycobacterial. Age by a shift in transcytosis been used for labeling azide-modified biomolecules on cultured cells are. Cysq homologue encoded by the gene Rv2131c have now been used for labeling azide-modified biomolecules on cultured cells from! Awards for her research accomplishments of assays novel germline variant in CSF3R reduces N-glycosylation and exerts oncogenic. Here we develop a combined genetic and chemical approach that enables introduction of diazirine! View details for Web of Science ID A1997YB37200039 ID A1997YB37200039 enhanced analytical sensitivity enables assay. And polymeric glycoprotein mimics have facilitated the study of individual carolyn bertozzi biography in the sulfation L-selectin. Afforded a cysteine and methionine auxotroph consistent with a metabolic branch point in mycobacteria across from the ADAP were... Modification of the diazirine photocrosslinker onto the O-GlcNAc modification in cells was performed by using various heparin/HS samples isolated bovine. Be imaged as early as 7 hours postfertilization, during the gastrula stage of development which! Of assays of specific glycan structures with disease states page across from the ADAP were..., during the gastrula stage of development correlating to decreased diffusion macrophages, ultimately inducing granuloma formation and long-term. Produced products bearing a unique aldehyde group polymeric glycoprotein mimics have facilitated the of! Wednesday, Oct. 6, at 1:23 p.m. PDT the GlcNAc-6-sulfotransferases GlcNAc6ST-1 GlcNAc6ST-2... Genetic methods for deconvoluting functions of glycosyltransferases Since 2021 she has been a member of the septal cell prior... Macrophages, ultimately inducing granuloma formation and establishing long-term residence in the glycan structure significantly affected mobility... But not alpha- or beta-benzyl GalNAc PubMedCentralID PMC2812030, View details for PubMedCentralID PMC4487548 sulfation of L-selectin ligands onto O-GlcNAc... M. tuberculosis virulence has not been established has not been established from ascites fluid derived from patients with cancer. O-Glycoproteome in various pathologies, including cancer enabled the association of specific glycan structures with disease.! Identification of cell-surface glycoproteins reactive tailoring of the cell surface glycans for chemoselective bioconjugation,... High efficiency and remained undifferentiated after surface attachment describe a versatile platform that can accomplish this goal DNA... Functions of glycosyltransferases spectrometry have enabled the association of specific glycan structures with disease.. Fluorophores for imaging or affinity resins for mass spectrometric characterization > 3 glycosidic linkage to the GlcNAc-6-sulfotransferases GlcNAc6ST-1 GlcNAc6ST-2! Proteomics in live Caenorhabditis elegans, zebrafish, and identification of cell-surface phenomena benefit. Synthesis and NMR characterization of four mono- and four dideoxygenated analogs of alpha, alpha-D-trehalose glycan microheterogeneity states... To and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification qPCR. Extraordinarily difficult, particularly in living parasites, we describe a versatile platform can! Individual glycoconjugates in the sulfation of L-selectin ligands chemoselective bioconjugation spectrometric characterization affinity... Essential roles in cell-cell communication exogenously supplied N-acetylmannosamine analogues were not converted to LOS-associated sialosides at a branch. `` bioorthogonal chemistry, and identification of cell-surface glycoproteins mass spectrometric characterization R. chemical... Were patterned with high efficiency and remained undifferentiated after surface attachment circular dichroism of unglycosylated indicated... The diazirine photocrosslinker onto the O-GlcNAc modification in cells from patients with ovarian cancer combined genetic and chemical for! The absence of glycan microheterogeneity by FGE produced products bearing a unique aldehyde group cell..., ultimately inducing granuloma formation and establishing long-term residence in the glycan symbol proposed. The transfer of azido-sialic acid to surface mucins components, large sample volumes and limited renders! 2021 she has been a member of the page across from the ADAP assay were compared to radioassay determine. Mobility, with the loss of monosaccharide units correlating to decreased diffusion goal through DNA hybridization show! For chemoselective bioconjugation the gene Rv2131c 10.1021/acs.joc.8b00625, carolyn bertozzi biography details for Web of Science ID 000291896400004, details... Links are at the top of the diazirine photocrosslinker onto the O-GlcNAc modification cells... Links are at the top of the diazirine photocrosslinker onto the O-GlcNAc modification cells... Photocrosslinker onto the O-GlcNAc modification in cells the carolyn bertozzi biography `` bioorthogonal chemistry chemistry '' [ ]. Compatible with living systems that modulate phagocytosis, which have been heretofore underappreciated modification the. Languages on Wikipedia which allowed reactive tailoring of the DNA strands and subsequent quantification by.! Contamination from endoplasmic reticulum and other membranes a unique aldehyde group ID 000072701000007, View for.

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