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. This approach can highlight changes in physiology or environment and may be more informative than steady-state analyses. 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. She described the reaction between the modified sugar and the fluorescent molecule as bioorthogonal. Poly-alpha2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. Disruption of cysH rendered Mtb auxotrophic for cysteine and methionine, and attenuated virulence in BALB/c and C57BL/6 immunocompetent mice. Grossman, H. L., Myers, W. R., Vreeland, V. J., Bruehl, R., Alper, M. D., Bertozzi, C. R., Clarke, J. Modular assembly of glycoproteins: Towards the synthesis of GlyCAM-1 by using expressed protein ligation, A strategy for functional proteomic analysis of glycosidase activity from cell lysates, Biomimetic engineering of carbon nanotubes by using cell surface mucin mimics. A., Solomon, E. I., Bertozzi, C. R. Formylglycine-generating enzyme binds substrate directly at a mononuclear Cu(I) center to initiate O2 activation. Martin, D. D., Vilas, G. L., Prescher, J. Here we develop a combined genetic and chemical approach that enables introduction of the diazirine photocrosslinker onto the O-GlcNAc modification in cells. Grand Challenges in Chemistry for 2016 and Beyond. View details for Web of Science ID 000168490400007, View details for Web of Science ID 000167717100191. Interactions of mucin glycoproteins with cognate receptors are dictated by the structures and spatial organization of glycans that decorate the mucin polypeptide backbone. Type I sulfatases require an unusual co- or post-translational modification for their activity in hydrolyzing sulfate esters. Surprisingly, Gal-1's effects on mammary patterning were independent of its glycan-binding ability and instead required localization within the nuclei of mammary epithelia. View details for DOI 10.1074/jbc.M510520200, View details for Web of Science ID 000235426200035. We labeled LAP fusion proteins expressed in living mammalian cells with Cy3, Alexa Fluor 568 and biotin. A key tool we developed for this study is a cell-permeable, small molecule inhibitor of GlcNAc 2-epimerase designed based on mechanistic principles. Saxon, E., Armstrong, J. I., Bertozzi, C. R. Cell surface engineering by a modified Staudinger reaction, Tyrosine sulfation: a modulator of extracellular protein-protein interactions, Discovery of carbohydrate sulfotransferase inhibitors from a kinase-directed library. Applications to the visualization of cellular glycans and enrichment of glycoproteins for proteomic analysis are described. Godula, K., Umbel, M. L., Rabuka, D., Botyanszki, Z., Bertozzi, C. R., Parthasarathy, R. Glycopeptide-preferring Polypeptide GalNAc Transferase 10 (ppGalNAc T10), Involved in Mucin-type O-Glycosylation, Has a Unique GalNAc-O-Ser/Thr-binding Site in Its Catalytic Domain Not Found in ppGalNAc T1 or T2. Seeliger, J. C., Topp, S., Sogi, K. M., Previti, M. L., Gallivan, J. P., Bertozzi, C. R. Thiacycloalkynes for Copper-Free Click Chemistry. From a panel of synthetic derivatives, we identified an azido GalNAc analog (N-azidoacetylgalactosamine, GalNAz) that is metabolized by numerous cell types and installed on mucin-type O-linked glycoproteins by the ppGalNAcTs. View details for Web of Science ID 000166039500060, View details for Web of Science ID 000165485300014. Carolyn R. Bertozzi, in full Carolyn Ruth Bertozzi, (born October 10, 1966, Boston, Massachusetts), American chemist known for her application of chemical synthesis to the study of biological systems. The azidofluorescein derivative also enabled cell imaging under no-wash conditions with good signal above background. Inactivation of the conserved steAB genes (cgp_1603-1604) was also found to confer EMB hypersensitivity and cell division defects. Enrichment of peptides derived from cytochrome c treated with the azide-containing cross-linker bis(succinimidyl)-3-azidomethyl glutarate (BAMG) shows several cross-link containing peptides. Using a green fluorescent protein-mucin fusion protein (SHGFP-MUC5AC/CK) as a FRAP (fluorescence recovery after photobleaching) probe, we have assessed in living mucous cells the relative importance of different protein post-translational modifications on the intragranular organization. A. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. Finally, we found that metabolic labeling of both cell envelope structures reports on drug effects on cell physiology in two hours, far faster than a genetic sensor of cell envelope stress. Both ordered tetrameric states emerge from clusters of the monomer phase, however, they then track along two different pathways. A., Shrager, J. Chang, P. V., Prescher, J. Bertozzi is a professor This Nel relaxation process is detected by the superconducting quantum interference device. Notably, labeling for (1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. This bifunctional microelectrode array is demonstrated for the pH monitoring and differentiation of primary T cells and Jurkat T lymphoma cells. Using azide-derivatized analogues of fucose, we metabolically labeled cell-surface glycans and then detected the incorporated azides via copper-free click chemistry with a difluorinated cyclooctyne probe. 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. The trend noted with solvent polarity is different and more revealing than that determined by the more classical approach of examining either the wavelength of the emission maximum or the fluorescence quantum yield. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. 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. In addition to carrying out a pivotal role in parasite persistence/replication within the infected mammal, the trans-sialidase is shed into the bloodstream and induces alterations in the host immune system by modifying the sialylation of the immune cells. Finally, the Delta papA2 and Delta papA1 mutants were screened for virulence defects in a mouse model of infection. These modified proteins integrated into the plasma membranes of a variety of mammalian cells and were internalized and directed to recycling endosomes similarly to GFP bearing a native GPI anchor. Expression of large tumour-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent growth factor signalling to support cell growth and survival. In previous work, we demonstrated that H. ducreyi scavenges sialic acid from the extracellular milieu and incorporates those residues into LOS. Yet, our understanding of the invivo ligands and function for most lectins is still incomplete. Surprisingly, the dibenzoselenacycloheptynes also abstracted hydrogen atoms from solvents such as THF or toluene, forming dibenzoselenacycloheptene products. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. Glycomic and glycoproteomic analyses via microarrays and mass spectrometry are beginning to characterize alterations in glycans that correlate with disease. View details for DOI 10.1038/s41467-019-12684-7. Because M. tuberculosis catabolizes host lipids to grow during infection, we propose that growth of M. tuberculosis on fatty acids in vivo leads to increased flux of MMCoA through lipid biosynthetic pathways, resulting in increased virulence lipid synthesis. This complex could be stored as a lyophilized powder and then dissociated in organic solvents to produce free DIFBO for in situ kinetic and spectroscopic analysis. View details for Web of Science ID 000304837800041. This technique, which is described in detail, provides a direct measurement of the energy that is released nonradiatively following photostimulation, and can therefore be used to indirectly determine the amount of energy released via luminescent pathways. Antibodies bind to and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. [10][11], Bertozzi was awarded the 2022 Nobel Prize in Chemistry, jointly with Morten P. Meldal and Karl Barry Sharpless, "for the development of click chemistry and bioorthogonal chemistry". As granuloma angiogenesis favors the infecting mycobacteria, it may be actively promoted by bacterial determinants during infection. 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. Her research group profiles changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and uses this information to develop new diagnostic and therapeutic approaches, most recently in the area of immuno-oncology. A step in this direction will be the development of tools to identify metabolites that share common structural features. Song, J., Xu, J., Filion, T., Saiz, E., Tomsia, A. P., Lian, J. View details for DOI 10.1021/jacs.6b12541, View details for PubMedCentralID PMC5345120. View details for DOI 10.1074/jbc.M109.017236, View details for Web of Science ID 000268097400064, View details for PubMedCentralID PMC2740463. Woo, C. M., Lund, P. J., Huang, A. C., Davis, M. M., Bertozzi, C. R., Pitteri, S. n. Imaging Mycobacterial Trehalose Glycolipids. Mucin-type O-linked glycosylation is a fundamental post-translational modification that is involved in a variety of important biological processes. 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. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in Mycobacterium smegmatis results in distinct host immune responses. View details for DOI 10.1073/pnas.1030024100, View details for Web of Science ID 000182939400099, View details for PubMedCentralID PMC156336. Here we present a unified design, based on the principle of photoinduced electron transfer, to access a panel of highly fluorogenic azide probes that are activated by conversion to the corresponding triazoles via click chemistry. The Cu(I)-catalyzed reaction was found to be most efficient for detecting azides in protein samples but was not compatible with live cells due to the toxicity of the reagents. Studies of 4Fe-4S cluster stability and cysteine reactivity in the presence and absence of substrates, and in the free enzyme versus the covalent enzyme-intermediate (E-Cys-S-SO(3)(-)), suggest a structural rearrangement that occurs during the catalytic cycle. Her lab focuses on profiling changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and exploiting this information for development of diagnostic and therapeutic approaches, most recently in the area of immuno-oncology. View details for DOI 10.1016/j.chembiol.2011.12.016, View details for Web of Science ID 000300917300009, View details for PubMedCentralID PMC3292763. Dr. Carolyn R. Bertozzi Ph.D. serves as Independent Director of the Company. View details for Web of Science ID 000179817000032, View details for Web of Science ID 000178916000001. Examples of sulfated metabolites as mediators of interactions between bacteria and plants suggest that sulfation is a key modulator of extracellular signaling between prokaryotes and eukaryotes. This new bioorthogonal process based on miniscule components is thus well-suited for activating molecules within cells under chemical control. Ac4GalNAz treatment labeled the surface of healthy mouse corneas, leaving most cells viable, and bacteria preferentially associated with GalNAz-labeled regions. Collectively, these chemical approaches are contributing great insight into the myriad biological functions of oligosaccharides. 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