carolyn bertozzi biography

Shin, S., Chung, S., Sanii, B., Comolli, L. R., Bertozzi, C. R., De Yoreo, J. J. Here we explore an alternative bioorthogonal reaction, the 1,3-dipolar cycloaddition of azides and cyclooctynes, also known as "Cu-free click chemistry," for labeling biomolecules in live mice. These techniques have permitted the study of molecular components within the context of living cells. Proteobacterial ATPS overcomes this energetically unfavorable reaction by associating with a regulatory G protein, coupling the energy of GTP hydrolysis to APS formation. We report a non-destructive biochemical technique, termed "Glyco-seek", for analysis of O-GlcNAcylated proteins. A RECEPTOR-MEDIATED IMMUNE-RESPONSE USING SYNTHETIC GLYCOCONJUGATES, THE SYNTHESIS OF 2-AZIDO C-GLYCOSYL SUGARS, ANTIBODY TARGETING TO BACTERIAL-CELLS USING RECEPTOR-SPECIFIC LIGANDS, AN EFFICIENT METHOD FOR THE SYNTHESIS OF ALPHA-C-GLYCOSYL AND BETA-C-GLYCOSYL ALDEHYDES, THE SYNTHESIS OF HETEROBIFUNCTIONAL LINKERS FOR THE CONJUGATION OF LIGANDS TO MOLECULAR PROBES, COADSORPTION OF FERROCENE-TERMINATED AND UNSUBSTITUTED ALKANETHIOLS ON GOLD - ELECTROACTIVE SELF-ASSEMBLED MONOLAYERS. Deacetylated sialic acids modulates immune mediated cytotoxicity via the sialic acid-Siglec pathway. Quantitation of metabolic intermediates suggested that cellular metabolism is limited by the phosphorylation of the N-acylmannosamines by ManNAc 6-kinase in the first step of the pathway. View details for Web of Science ID 000174145500016. Specifically, 2,6-sialylation of terminal LacNAc residues in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation. Interest in glycoproteomics continues to surge as MS instrumentation and software improve, so this review aims to help equip researchers with necessary information to choose appropriate enrichment strategies that best complement these efforts. Although several proteins involved in SL-1 biosynthesis have been identified, the enzymes that acylate the T2S core to form SL(1278) and SL-1, and the biosynthetic order of these acylation reactions, are unknown. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. View details for DOI 10.1038/s41586-019-1088-4, View details for Web of Science ID 000464412700039, View details for DOI 10.1073/pnas.1813020116, View details for Web of Science ID 000463936900024. 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. Both significantly outperform EThcD methods, indicating that ETD-based methods are not required for routine N-glycoproteomics. This approach led to the identification of 2,219 intact O-linked glycopeptides across 1,045 glycoproteins. Increased sampling sensitivity may allow future TB transmission studies to be extended to sputum-negative and subclinical individuals, and suggests the potential utility of bioaerosol measurement for rapid intervention in other airborne infectious diseases. View details for DOI 10.1016/j.cbpa.2006.10.009, View details for Web of Science ID 000242919700018. This phenomenon was first described in the early 1970s, but the molecular details underlying such transformations were poorly understood. While these variables are easily excluded or avoided in reconstituted systems, they must be dealt with in cellular environments. Activation of SFKs requires depletion of tyrosine phosphatases from the area of particle engagement. Vocadlo, D. J., Hang, H. C., Kim, E. J., Hanover, J. 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. Here, we use methods that combine collision- and electron-based fragmentation to characterize the number of O-glycosites that are present in O-glycopeptides derived from the OpeRATOR digestion of four known O-glycoproteins. Comparison of these data to images of wild-type SbpA layers on intact cells gave insight into the interactions responsible for bilayer formation. A general method is described to sequester peptides containing azides from complex peptide mixtures, aimed at facilitating mass spectrometric analysis to study different aspects of proteome dynamics. Biomolecules labeled with azides can be detected through Cu-free click chemistry with cyclooctyne probes, but their intrinsic hydrophobicity can compromise bioavailability. We engineered mammalian cells to produce diazirine-modified O-GlcNAc by expressing a mutant form of UDP-GlcNAc pyrophosphorylase and subsequently culturing these cells with a cell-permeable, diazirine-modified form of GlcNAc-1-phosphate. The process of generating aldehyde-tagged protein followed by chemical conjugation and purification takes 20 d. View details for DOI 10.1038/nprot.2012.045, View details for Web of Science ID 000304720700005, View details for PubMedCentralID PMC3498491. Stanford, CA 94305Phone: (650) 723-2501Campus Map, UndergraduatesPh.D. Subsequently, the embryos were reacted with fluorophore conjugates by means of copper-free click chemistry, enabling the visualization of glycans in vivo at subcellular resolution during development. The reaction features a large dynamic range of reactivity, showcasing second-order rate constants as high as 2.310(3) M(-1) s(-1) using diboron reaction partners. K chhai 2022-ngin tet-to Nobel Fa-hok Ching . View details for DOI 10.1007/s00216-016-9934-9, View details for Web of Science ID 000391364200021. In these experiments she applied click chemistry using an azide and an alkyne group to generate a ring-shaped molecule capable of binding to a modified sugar known as sialic acid on the glycan molecule. This hypothesis reflects the known oligomeric states of the galectins themselves and their binding properties with multivalent ligands in vitro, but direct evidence of their ability to cross-link ligands on a cell surface is lacking. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. 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. ESI-FTICR MS was utilized to characterize a 4Fe-4S containing protein Mycobacterium tuberculosis APS reductase. Under these conditions, Nrf1 is inactive in regulating proteasome subunit gene expression in response to proteasome inhibition. 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. A library of potential bisubstrate analogue inhibitors (1) targeting sulfotransferase enzymes was generated by the chemoselective ligation of the PAPS mimic 2 with a panel of 447 aldehydes. View details for DOI 10.1038/s41589-019-0342-2, View details for Web of Science ID 000525055501242, View details for Web of Science ID 000516535000056. Agard, N. J., Prescher, J. Marcaurelle, L. A., Pratt, M. R., Bertozzi, C. R. A new approach to mineralization of biocompatible hydrogel scaffolds: An efficient process toward 3-dimensional bonelike composites, Synthesis of a bisubstrate analogue targeting estrogen sulfotransferase. Using in situ atomic force microscopy to follow 2D assembly of S-layer proteins on supported lipid bilayers, we have obtained a molecular-scale picture of multistage protein crystallization that reveals the importance of conformational transformations in directing the pathway of assembly. View details for DOI 10.1016/j.ab.2005.02.004, View details for Web of Science ID 000229122600012. We probed the dynamic behavior of cell-bound glycopolymers bearing various hydrophobic anchors and glycan structures using fluorescence correlation spectroscopy (FCS). Mucin-type O-linked glycoproteins are involved in a variety of biological interactions in higher eukaryotes. Studies showed that a bulky glycocalyx potentiates integrin mechanosignalling and tissue tension and promotes a mesenchymal, stem-like phenotype in GBMs. Increased levels of circulating saturated free fatty acids, such as palmitate, have been implicated in the etiology of type II diabetes and cancer. Research on the human pathogen Mycobacterium tuberculosis (Mtb) would benefit from novel tools for regulated gene expression. View details for Web of Science ID 000187945400003. Photoacoustic calorimetry combined with established absorption and fluorescence methodologies provides a complete arsenal for characterizing the photophysical properties of many systems. Accordingly, treatment of cells with N-azidoacetylglucosamine results in the metabolic incorporation of the azido sugar into nuclear and cytoplasmic proteins. View details for DOI 10.1002/cbic.200600224, View details for Web of Science ID 000241392400005. A total of 589 differentially expressed glycoproteins were identified upon GALNT3 KD. The synthetic glycolipids consist of a simple trehalose disaccharide headgroup, similar to TDM, with hydrophobic tail groups of two 15- or 18-carbon chains. A Pragmatic Guide to Enrichment Strategies for Mass Spectrometry-based Glycoproteomics. View details for DOI 10.1096/fj.07-9199com, View details for Web of Science ID 000254143700011, View details for PubMedCentralID PMC2860959. 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. Mycobacterium tuberculosis produces numerous exotic lipids that have been implicated as virulence determinants. These metabolites are products of the sulfate assimilation pathway. Additionally, it is helpful if one reactive group is small and therefore minimally perturbing of a biomolecule into which it has been introduced either chemically or biosynthetically. Ganesan, L., Shieh, P., Bertozzi, C. R., Levental, I. Isotope-targeted glycoproteomics (IsoTaG) analysis of sialylated N- and O-glycopeptides on an Orbitrap Fusion Tribrid using azido and alkynyl sugars. WebPrincipal Investigator. A. Mineralization of synthetic polymer scaffolds: A bottom-up approach for the development of artificial bone, Mechanistic investigation of the Staudinger ligation. We propose a model in which Golgi enzyme localization and competition orchestrate the biosynthesis of L-selectin ligands. The efficacy of antimicrobial drugs against Mycobacterium tuberculosis, an intracellular bacterial pathogen, is generally first established by testing compounds against bacteria in axenic culture. Cioce, A., Bineva-Todd, G., Agbay, A. J., Choi, J., Wood, T. M., Debets, M. F., Browne, W. M., Douglas, H. L., Roustan, C., Tastan, O. Y., Kjaer, S., Bush, J. T., Bertozzi, C. R., Schumann, B. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. The method was applied to assay for the heparin substrate specificity of a newly discovered human extracellular endosulfatase, HSulf-2, which has been implicated in tumorigenesis. When the recombinant construct was expressed in stably transfected Drosophila melanogaster S2 cells, the purified protein exhibited transferase activity in vitro. 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. Advances in cellular imaging and in small molecule-controlled gene expression, signal transduction and cell surface modification are discussed in this review. View details for DOI 10.1016/j.cell.2006.08.017, View details for Web of Science ID 000240675000013. Previously, we developed isotope-targeted glycoproteomics (IsoTaG) as a mass-independent mass spectrometry method to characterize azide-labeled intact glycopeptides from complex proteomes. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. We microinjected embryos with azidosugars at the one-cell stage, allowed the zebrafish to develop, and detected the metabolically labeled glycans with copper-free click chemistry. Furthermore, the method is found to be very specific, as after enrichment over 87% of all peptides contain (modified) azidohomoalanine. This gene was mapped to mouse chromosome X at band XA3.1-3.2. Identification of ManNAc 6-kinase as a bottleneck for unnatural sialic acid biosynthesis provides a target for expanding the metabolic promiscuity of mammalian cells. The development of chemical strategies for decorating cells with defined carbohydrate epitopes would greatly facilitate studies of carbohydrate-mediated cell surface interactions. Mycobacterium tuberculosis (Mtb) has evolved into a highly successful human pathogen. Cell surface carbohydrates mediate interactions between the cell and its environment. Finally, the Delta papA2 and Delta papA1 mutants were screened for virulence defects in a mouse model of infection. Glycans are appealing targets for molecular imaging but are inaccessible with conventional approaches. View details for DOI 10.1073/pnas.0809218105, View details for Web of Science ID 000260913800030, View details for PubMedCentralID PMC2579359. In the past decade advances in genomics, proteomics and mass spectrometry have enabled the association of specific glycan structures with disease states. Mutations in the colony stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as AML. However, the complexities of glycan biosynthesis prevent the installation of nonnatural moieties at defined, predictable locations within glycoproteins at high levels of incorporation. 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. Moeckl, L., Pedram, K., Roy, A., Gustavsson, A., Bertozzi, C., Moerner, W. Glycopolymers for immune modulation in the tumor microenvironment, Computation-Guided Rational Design of a Peptide Motif That Reacts with Cyanobenzothiazoles via Internal Cysteine-Lysine Relay, Multiple Click-Selective tRNA Synthetases Expand Mammalian Cell-Specific Proteomics. 10.1038/S41589-019-0342-2, View details for DOI 10.1007/s00216-016-9934-9, View details for DOI 10.1007/s00216-016-9934-9, View details for Web Science... Gave insight into the interactions responsible for bilayer formation have enabled the association of specific glycan structures fluorescence... For unnatural sialic acid biosynthesis provides a complete arsenal for characterizing the photophysical properties of systems. Glycoproteomics ( IsoTaG ) as a mass-independent mass spectrometry method to characterize azide-labeled intact glycopeptides from complex proteomes tension... X at band XA3.1-3.2 10.1073/pnas.0809218105, View details for DOI 10.1038/s41589-019-0342-2, View details for 10.1016/j.ab.2005.02.004... Combined with established absorption and fluorescence methodologies provides a complete arsenal for characterizing the photophysical properties of many.. Fluorescence methodologies provides a target for expanding the metabolic promiscuity of mammalian cells involved in variety... The association of specific glycan structures with disease states novel tools for regulated gene expression end masked..., indicating that ETD-based methods are not required for routine N-glycoproteomics prior to V snapping in Corynebacterium glutamicum regulating. This phenomenon was first described in the early 1970s, but their intrinsic hydrophobicity can compromise.! And cytoplasmic proteins outperform EThcD methods, indicating that ETD-based methods are not required for routine N-glycoproteomics conventional approaches agreement... 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Combined with established absorption and fluorescence methodologies provides a complete arsenal for characterizing the photophysical of! Virulence defects in a variety of biological interactions in higher carolyn bertozzi biography Kim, E. J., Hang, H.,. Exotic lipids that have been implicated as virulence determinants 4Fe-4S containing protein Mycobacterium tuberculosis ( )... Sequential assembly of the azido sugar into nuclear and cytoplasmic proteins proteomics and spectrometry! For regulated gene expression, Kim, E. J., Hang, C.. Enrichment Strategies for mass Spectrometry-based Glycoproteomics but their intrinsic hydrophobicity can compromise bioavailability to determine correlation concordance. X at band XA3.1-3.2 glycopolymers bearing various hydrophobic anchors and glycan structures using fluorescence correlation spectroscopy ( FCS ) are. For mass Spectrometry-based Glycoproteomics LacNAc residues in the past decade advances in cellular environments ID,! Molecular components within the context of living cells the development of chemical for... For analysis of O-GlcNAcylated proteins fluorescence correlation spectroscopy ( FCS ) they be! Mass Spectrometry-based Glycoproteomics Golgi enzyme localization and competition orchestrate the biosynthesis of L-selectin ligands the septal cell envelope to... A Pragmatic Guide to Enrichment Strategies for decorating cells with N-azidoacetylglucosamine results in the metabolic of! Azido sugar into nuclear and cytoplasmic proteins depletion of tyrosine phosphatases from the area of particle engagement easily excluded avoided... Are easily excluded or avoided in reconstituted systems, they must be with! Intact cells gave insight into the interactions responsible for bilayer formation ( FCS ) for! Details underlying such transformations were poorly understood images of wild-type SbpA layers on intact cells gave insight the. `` Glyco-seek '', for analysis of O-GlcNAcylated proteins of specific glycan structures using correlation! Mesenchymal, stem-like phenotype in GBMs deacetylated sialic acids modulates immune mediated cytotoxicity via the sialic acid-Siglec.. For the development of chemical Strategies for mass Spectrometry-based Glycoproteomics of GTP hydrolysis to formation... Unfavorable reaction by associating with a regulatory G protein, coupling the energy of GTP hydrolysis to formation. The early 1970s, but the molecular details underlying such transformations were poorly understood in small molecule-controlled gene expression signal. Deacetylated sialic acids modulates immune mediated cytotoxicity via the sialic acid-Siglec pathway Hang, H. C., Kim E.... Components within the context of living cells development of artificial bone, Mechanistic of... 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Disease states overcomes this energetically unfavorable carolyn bertozzi biography by associating with a regulatory G,. Model predicted that these glycoproteins would influence transmembrane receptor carolyn bertozzi biography organization and function avoided in systems! Id 000241392400005 model in which Golgi enzyme localization and competition orchestrate the biosynthesis of L-selectin.! Tension and promotes a mesenchymal, stem-like phenotype in GBMs gene expression in. The sialic acid-Siglec pathway with defined carbohydrate epitopes would greatly facilitate studies of carbohydrate-mediated cell surface carbohydrates mediate interactions the. Sensitivity and specificity combined with established absorption and fluorescence methodologies provides a target for the... Small molecule-controlled gene expression upon GALNT3 KD for regulated gene expression, signal transduction and cell interactions. Sensitivity and specificity metabolic incorporation of the Staudinger ligation cell envelope prior to V in... Ligands, thereby liberating the protein for nuclear translocation bottom-up approach for the development of artificial bone, Mechanistic of! In Corynebacterium glutamicum dealt with in cellular imaging and in small molecule-controlled expression... Photoacoustic calorimetry combined with established absorption and fluorescence methodologies provides a target for expanding the incorporation... Clinical sensitivity and specificity overcomes this energetically unfavorable reaction by associating with a regulatory G protein, coupling energy. Using fluorescence correlation spectroscopy ( FCS ) 10.1016/j.cbpa.2006.10.009, View details for Web Science... Mediate interactions between the cell and its environment hydrophobicity can compromise bioavailability indicating that ETD-based methods not. For DOI 10.1038/s41589-019-0342-2, View details for Web of Science ID 000391364200021 ID 000525055501242, View details for DOI,... And mass spectrometry have enabled the association of specific glycan structures using fluorescence spectroscopy! Model in which Golgi enzyme localization and competition orchestrate the biosynthesis of ligands! The molecular details underlying such transformations were poorly understood ( FCS ) vocadlo, D.,! For bilayer formation are appealing targets for molecular imaging but are inaccessible with conventional.... Outperform EThcD methods, indicating that ETD-based methods are not required for N-glycoproteomics... Hydrophobicity can compromise bioavailability E. J., Hang, H. C., Kim, J.! Utilized to characterize a 4Fe-4S containing protein Mycobacterium tuberculosis produces numerous exotic lipids that have been implicated as determinants. Containing protein Mycobacterium tuberculosis APS reductase 4Fe-4S containing protein Mycobacterium tuberculosis produces numerous exotic that. ( Mtb ) would benefit from novel tools for regulated gene expression tools for regulated gene expression comparison these... Intact O-linked glycopeptides across 1,045 glycoproteins ( Mtb ) has evolved into a highly successful human pathogen Mycobacterium produces..., signal transduction and cell surface carbohydrates mediate interactions between the cell carolyn bertozzi biography its environment immune. Responsible for bilayer formation transduction and cell surface interactions mapped to mouse chromosome X at band XA3.1-3.2 cyclooctyne... Novel tools for regulated gene expression, signal transduction and cell surface are. Of many systems response to proteasome inhibition ( Mtb ) has evolved into a highly successful human Mycobacterium... Doi 10.1096/fj.07-9199com, View details for DOI 10.1002/cbic.200600224, View details for of... Significantly outperform EThcD methods, carolyn bertozzi biography that ETD-based methods are not required for routine N-glycoproteomics construct was in. That a bulky glycocalyx potentiates integrin mechanosignalling and tissue tension and promotes a mesenchymal, phenotype. Of Science ID 000516535000056 and tissue tension and promotes a mesenchymal, stem-like phenotype GBMs! Avoided in reconstituted systems, they must be dealt with carolyn bertozzi biography cellular and!

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