Our findings suggest that there is a dynamic and reciprocal link between integrin mechanosignalling and a bulky glycocalyx, implying a causal link towards a mesenchymal, stem-like phenotype in GBMs. View details for Web of Science ID A1994NH63300010. Yet, our understanding of the invivo ligands and function for most lectins is still incomplete. However, the lack of chemical tools to study mucin-type O-linked glycosylation has hindered our molecular understanding of O-linked glycans in many biological contexts. WebDr. View details for DOI 10.1021/acscentsci.6b00070, View details for PubMedCentralID PMC4827488. View details for DOI 10.1016/j.carres.2007.05.009, View details for Web of Science ID 000249191300005, View details for PubMedCentralID PMC2072868. View details for DOI 10.1021/acs.analchem.0c02950. Mucin biology has been difficult to study at the molecular level, in part, because methods to manipulate and structurally characterize mucin domains are lacking. Thus, BARAC is a promising reagent for in vivo imaging. Investigations into the roles of protein glycosylation have revealed functions such as modulating protein structure and localization, cell-cell recognition, and signaling in multicellular systems. The key building block was a 2-azido-3-thiogalactose-Thr analogue that was incorporated into a peptide by fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. View details for Web of Science ID 000338992200029. View details for Web of Science ID 000229578100018. We show that the enhanced analytical sensitivity enables this assay to correctly identify HIV-infected individuals otherwise missed by current OF assays. They write new content and verify and edit content received from contributors. Cells bend their plasma membranes into highly curved forms to interact with the local environment, but how shape generation is regulated is not fully resolved. View details for Web of Science ID 000263320900008, View details for PubMedCentralID PMC2709987. We present IsoTaG, a mass-independent chemical glycoproteomics platform for characterization of intact, metabolically labeled glycopeptides at the whole-proteome scale. Biosynthesis and Regulation of Sulfomenaquinone, a Metabolite Associated with Virulence in Mycobacterium tuberculosis. Preliminary screening has identified compounds that inhibit estrogen sulfotransferase (EST), an enzyme relevant to breast cancer. An essential step in this pathway is the activation of sulfate through adenylation by the enzyme ATP sulfurylase (ATPS), forming adenosine 5'-phosphosulfate (APS). Luchansky, S. J., Yarema, K. J., Takahashi, S., Bertozzi, C. R. Synthesis of thioether-linked analogues of the 2,3-sialyl-TF and MECA-79 antigens: Mucin-type glycopeptides associated with cancer and inflammation. Her biography is available in 16 different languages on Wikipedia. She coined the Furthermore, we show that these mimetics enhance the survival of nonmalignant cells in a zebrafish model of metastasis. A., Mills, J. R., Roforth, M. M., Pittock, S. J., McKeon, A., Page, K., Wolf, W. A., Sanda, S., Speake, C., Greenbaum, C. J., Tsai, C. Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells. View details for Web of Science ID 000187945400003. The generation of homogeneously glycosylated proteins is essential for defining glycoform-specific activity and improving protein-based therapeutics. Mucin-type O-linked glycoproteins are involved in a variety of biological interactions in higher eukaryotes. Laureates [3] [ edit] Laureates per country [ edit] Second, we evaluated a panel of five different cyclooctyne structures and found that fluorophore conjugates to aza-dibenzocyclooctyne (ADIBO) gave the highest and most specific derivatization of azide-conjugated LAP in cells. The polyvalent display of carbohydrate groups found on cell surface glycoprotein structures may contribute to the enhanced binding strength of selectin-mediated adhesion. View details for Web of Science ID 000280227700012, View details for PubMedCentralID PMC2907714. The inducible riboswitch platform has the potential to be a powerful general strategy for creating customized gene regulation systems in Mtb. In the 1990s, Dr. Bertozzi was studying glycans, carbohydrates that sit on the surfaces of proteins and cells, the functions of which were not wholly understood. 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. O-GlcNAc transferase (OGT) catalyzes the addition of N-acetylglucosamine (O-GlcNAc) onto a diverse array of intracellular proteins. Methods for targeting of small molecules to cellular proteins can allow imaging with fluorophores that are smaller, brighter, and more photostable than fluorescent proteins. 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. Mougous, J. D., Leavell, M. D., Senaratne, R. H., Leigh, C. D., Williams, S. J., Riley, L. W., Leary, J. Fluorescent bioorthogonal smart probes across the visible spectrum will enable sensitive visualization of metabolically labeled molecules in biological systems. The lack of a defined consensus sequence for the ppGalNAcTs makes the prediction of mucin-type O-linked glycosylation difficult based on primary sequence alone. Cell surface carbohydrates mediate interactions between the cell and its environment. 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. Methods for the controlled derivatization of glycoproteins are presently limited by the repertoire of natural amino acid side chain and carbohydrate functionalities. We hope this review will inspire biologists to make use of these new techniques and stimulate chemists to continue developing innovative approaches to probe lectin biology invivo. View details for DOI 10.1074/mcp.M600314-MCP200, View details for Web of Science ID 000242852000012. 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. Herein we report a semisynthetic method of producing membrane-anchored proteins. As part of the quest for new gold drugs, we have explored the efficacy of three gold complexes derived from the tuberculosis drug pyrazinamide (PZA), namely, the gold(I) complex [Au(PPh3)(PZA)]OTf (1, OTf = trifluoromethanesulfonate) and two gold(III) complexes [Au(PZA)Cl2] (2) and [Au(PZO)Cl2] (3, PZO = pyrazinoic acid, the metabolic product of PZA) against two mycobacteria, Mycobacterium tuberculosis and Mycobacterium smegmatis. Azide-labeled proteins are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization. Here we use high-resolution, high-mass-accuracy, and tandem mass spectrometry to characterize the structure of S881. The cysH mutant was also susceptible to peroxynitrite and hydrogen peroxide in vitro. 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 protocol, we describe a novel mass-independent chemical glycoproteomics platform for characterizing intact, metabolically labeled glycopeptides from complex proteomes, termed Isotope Targeted Glycoproteomics (IsoTaG). Recently, several M. tuberculosis mutants were tested as potential vaccine candidates in the mouse model of tuberculosis. Together, these data reveal a mechanism by which PcaA-mediated cis-cyclopropanation of mycolic acids promotes bacterial growth and dissemination invivo by eliciting granuloma vascularization and suggest potential approaches for host-directed therapies. Thus, cell surface ketones are a potential vehicle for a metabolically controlled small-molecule drug delivery system. and Irmgard Chu Distinguished Professorship in Chemistry, 2007 LGBTQ Scientist of the Year Award from the, 2008 Li Ka Shing Women in Science Award, 2008 Roy L. Whistler International Award in Carbohydrate Chemistry, 2009 Albert Hofmann Medal, Univ. Nessen, M. A., Kramer, G., Back, J., Baskin, J. M., Smeenk, L. E., de Koning, L. J., van Maarseveen, J. H., de Jong, L., Bertozzi, C. R., Hiemstra, H., de Koster, C. G. Direct Cell Surface Modification with DNA for the Capture of Primary Cells and the Investigation of Myotube Formation on Defined Patterns. The coating layers of macrophages and their targets hinder phagocytosis by both steric and electrostatic means. Here we investigate the conversion of a panel of azide-functionalized mannosamine and glucosamine derivatives into cell-surface sialosides. The GPI-protein analogs also diffused freely in cellular membranes. The rv3406 strain did not replicate in minimal media with 2-ethyl hexyl sulfate as the sole sulfur source, in contrast to wild type Mtb or the complemented strain. While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. Schilling, B., Goon, S., Samuels, N. M., Gaucher, S. P., Leary, J. Consequently, we developed a nonradioactive detection methodology in which a bio-orthogonal azidomyristate analog is specifically incorporated co- or post-translationally into proteins at N-terminal glycines, chemoselectively ligated to tagged triarylphosphines and detected by Western blotting with short exposure times (seconds to minutes). A. However, the synthetic difficulties inherent to sialylated and fucosylated oligosaccharides motivate the search for alternative antagonists. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated N-azidoacetylgalactosamine (Ac4GalNAz). View details for DOI 10.1038/NCHEMBIO.2076, View details for Web of Science ID 000376160600017, View details for PubMedCentralID PMC4871776, View details for DOI 10.1021/acscentsci.6b00102, View details for PubMedCentralID PMC4850509. She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. In this paper, we report on a general synthetic strategy for the assembly of glycopolymers that capitalizes on the intrinsic reactivity of reducing glycans toward hydrazides to form stable cyclic N-glycosides. View details for DOI 10.1128/AAC.47.1.378-382.2003, View details for Web of Science ID 000180149600058, View details for PubMedCentralID PMC148999, View details for DOI 10.1016/S0955-2219(03)00302-9, View details for Web of Science ID 000185381600023. Approximately one thousand proteins are annotated as being palmitoylated, and for some of these, including several oncogenes of the Ras and Src families, palmitoylation is indispensable for protein function. We use a novel fractionation procedure to demonstrate that SL-1 is present on the cell surface, whereas SL(1278) is found exclusively in more internal layers. The expanding integrin wave facilitates the zippering of Fc receptors onto the target and integrates the information from sparse receptor-ligand complexes, coordinating the progression and ultimate closure of the phagocytic cup. View details for Web of Science ID 000077136900049, View details for Web of Science ID 000076649700013, View details for Web of Science ID 000075884200020. For example, chemical glycoproteomics technologies have enabled the identification of specific glycosylation sites and glycan structures that modulate protein function in a number of biological processes. Stanford chemist Carolyn Bertozzi was awarded the Nobel Prize in chemistry for her development of bioorthogonal reactions, which allow scientists to explore cells and track biological processes without disrupting the normal chemistry of the cell. The difference in preferred substrates between L-selectin and MECA-79 may explain the variable activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial venules in lymphoid organs. The advantage of this ELISA over previous assays is that a macromolecular physiological ligand is employed, rather than a fortuitous or simplified carbohydrate ligand. Nijmegen (2013), Honorary Doctorate Degree, Brown University (2012), Tetrahedron Young Investigator Award, Executive Board of Editors and the Publisher of Tetrahedron Publications (2011), Harrison Howe Award, Rochester Section, American Chemical Society (2009), W. H. Nichols Award, New York Section, American Chemical Society (2009), Li Ka Shing Women in Science Award, Li Ka Shing Foundation Women in Science Program (2008), Roy L. Whistler International Award in Carbohydrate Chemistry, International Carbohydrate Organization (2008), Willard Gibbs Medal, Chicago Section, American Chemical Society (2008), T.Z. and Kirk Schanze and Lee, {T. Randall} and Lutkenhaus, {Jodie L.} and David Kaplan and Christopher Jones and Carolyn Bertozzi and Laura Kiessling and Mulcahy, {Mary Beth} and Lindsley, {Craig W.} and Finn, {M. G.} and Blum, {Joel D.} and Prashant Kamat and The search for alternative antagonists ( o-glcnac ) onto a diverse array of intracellular proteins and derivatives... Susceptible to peroxynitrite and hydrogen peroxide in vitro glycopeptides at the whole-proteome scale DOI 10.1016/j.carres.2007.05.009, View details DOI... To study mucin-type O-linked glycosylation difficult based on primary sequence alone function for most is... 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