Our results suggest that both Gal-6-SO(4) and GlcNAc-6-SO(4) may contribute to L-selectin recognition, either as components of sulfosialyl-Le(X) capping groups or in internal structures. Chang, P. V., Chen, X., Smyrniotis, C., Xenakis, A., Hu, T., Bertozzi, C. R., Wu, P. Quantitative Proteomic Profiling of Host-Pathogen Interactions: The Macrophage Response to Mycobacterium tuberculosis Lipids. Putative Mtb bacilli were detected in collected fluid by fluorescence microscopy utilising DMN-Trehalose. In addition, GalNAz efficiently labeled mucin-type O-linked glycoproteins expressed at endogenous levels. We treated worms with azidosugar variants of N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), and N-acetylmannosamine (ManNAc), resulting in the metabolic labeling of their cell-surface glycans with azides. As granuloma angiogenesis favors the infecting mycobacteria, it may be actively promoted by bacterial determinants during infection. Metabolic labeling of recombinant interferon-beta and GlyCAM-Ig was achieved, demonstrating the utility of the method for functionalizing N-linked and O-linked glycoproteins of therapeutic interest. Cyclooctyne reagents have now been used for labeling azide-modified biomolecules on cultured cells and in live Caenorhabditis elegans, zebrafish, and mice. Together, localisation and association govern the assembly of complex glycans and thereby regulate interactions at the cell surface. Erik Gregersen is a senior editor at Encyclopaedia Britannica, specializing in the physical sciences and technology. View details for DOI 10.1074/mcp.M111.015339, View details for Web of Science ID 000306408500017. Flynn, R. A., Belk, J. The inhibitory activity of 1-68A and a panel of synthetic analogues identified moieties necessary for inhibition. Noncovalent complexes of the holoprotein with several ligands, including APS, thioredoxin, and AMP, were also investigated. The quadricyclane ligation joins a small but growing list of tools for the selective covalent modification of biomolecules. In the ligation reaction, the intermediate aza-ylide undergoes intramolecular reaction with an ester, forming an amide bond faster than aza-ylide hydrolysis would otherwise occur in water. A novel germline variant in CSF3R reduces N-glycosylation and exerts potent oncogenic effects in leukemia. 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. 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 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 10.1016/j.chembiol.2015.07.009, View details for PubMedCentralID PMC4567249, View details for DOI 10.1021/acscentsci.5b00245, View details for PubMedCentralID PMC4827477. Recognized for its roles in membrane tethering, cellular signaling, and protein trafficking, palmitoylation is also emerging as a potential regulator of metabolism. However, little work has been devoted to understanding their effects on the physiology of the cell envelope, one of the main targets of this clinical regimen. Bowman, K. G., Hemmerich, S., Bhakta, S., SINGER, M. S., Bistrup, A., ROSEN, S. D., Bertozzi, C. R. Chemical approaches to glycobiology and emerging carbohydrate-based therapeutic agents, A strategy for the chemoselective synthesis of O-linked glycopeptides with native sugar-peptide linkages. Sheta, R., Woo, C. M., Roux-Dalvai, F., Fournier, F., Bourassa, S., Droit, A., Bertozzi, C. R., Bachvarov, D. Click-EM for imaging metabolically tagged nonprotein biomolecules. This may be a result of BPA sulfation/desulfation providing a pathway for selective uptake into hormone-responsive cells. We fed cells an unnatural monosaccharide, a modified mannosamine that replaced the acetyl group with a levulinate group (ManLev). Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7. Collectively, these chemical approaches are contributing great insight into the myriad biological functions of oligosaccharides. Human embryonic stem cells were found to have high levels of high mannose glycans, which contrasts with IMR-90 fibroblasts and a human normal breast cell line, where complex glycans are by far the most abundant and high mannose glycans are minor components. Shin, S., Comolli, L. R., Tscheliessnig, R., Wang, C., Ki Tae Nam, K. T., Hexemer, A., Siegerist, C. E., De Yoreo, J. J., Bertozzi, C. R. D-Amino Acid Chemical Reporters Reveal Peptidoglycan Dynamics of an Intracellular Pathogen. Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. A., Bertozzi, C. R. Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation. Consequently, growth on this substrate required the transcriptional induction of the propionyl-CoA-assimilating methylcitrate cycle (MCC) enzymes, via the Rv1129c regulatory protein. Each enzyme preferred a terminal GlcNAc residue, and was impeded by the addition of a beta1,4-linked Gal residue (i.e., terminal LacNAc). Because the parameters which govern this effect are well understood and are amenable to chemical modification, this knowledge may enable the rational development of more effective antibiotics against tuberculosis. In this review, we describe the important role that chemical glycoproteomics methods are playing in such efforts. A., Sletten, E. M., Bertozzi, C. R., Popik, V. V., Ting, A. Y. We describe a method for modifying proteins site-specifically using a chemoenzymatic bioconjugation approach. Proteobacterial ATPS overcomes this energetically unfavorable reaction by associating with a regulatory G protein, coupling the energy of GTP hydrolysis to APS formation. The importance and complexity associated with the totality of glycan structures, i.e. Tests against related enzymes confirmed the compound's specificity for the UDP-GlcNAc 4-epimerase. Polysialyltransferases catalyze the glycosylation of the neural cell adhesion molecule (NCAM) with polysialic acid (PSA). This heterogeneity precludes enrichment strategies that can be universally beneficial for all glycan classes. We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell. Sialic acids are a family of related sugars that play essential roles in many biological events intimately linked to cellular recognition in both health and disease. This review discusses the structural diversity of the GPI anchor and its putative cellular functions, including involvement in lipid raft partitioning, signal transduction, targeting to the apical membrane, and prion disease pathogenesis. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is presented. Mucin-type O-linked glycoproteins are involved in a variety of biological interactions in higher eukaryotes. The identification of this enzyme in T. gondii demonstrates that this human parasite has its own enzymatic machinery for the O-glycosylation of toxoplasmal proteins. We refer to these fascinating structures as "carbon nanohoops" due to their structural similarity to carbon nanotubes. 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. These results shed light on the physical barriers that modulate phagocytosis, which have been heretofore underappreciated. Glycans also present a rich matrix of information that adapts rapidly to changing environs. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. Yu, S., Boyce, M., Wands, A. M., Bond, M. R., Bertozzi, C. R., Kohler, J. J. Elucidation and Chemical Modulation of Sulfolipid-1 Biosynthesis in Mycobacterium tuberculosis. A comparative study of bioorthogonal reactions with azides. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. Molecules terminated with Texas Red lie flat at the membrane (height, 0 +/- 2 nm), implying that interactions between Texas Red and the bilayer dominate the polymers' free energy. View details for DOI 10.1074/jbc.M304928200, View details for Web of Science ID 000185713800121. Mucin domains are densely O-glycosylated modular protein domains that are found in a wide variety of cell surface and secreted proteins. The first synthesis and characterization of [9]-, [12]-, and [18]cycloparaphenylene was demonstrated utilizing a novel aromatization reaction. 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. New developments have allowed researchers to begin probing the inner workings of the cell to gain new insight into cell function and metabolism. These observations suggest crosstalk between autophagy and phagocytosis that may be relevant to the innate immune response of macrophages. View details for DOI 10.1074/mcp.M600314-MCP200, View details for Web of Science ID 000242852000012. Here, we report a technique for rapid profiling of O-linked glycoproteins in living animals by metabolic labeling with N-azidoacetylgalactosamine (GalNAz) followed by Staudinger ligation with phosphine probes. View details for Web of Science ID 000245946400051, View details for PubMedCentralID PMC2535821. A mineralization technique was developed that exposes carboxylate groups on the surface of cross-linked pHEMA, promoting high-affinity nucleation and growth of calcium phosphate on the surface, along with extensive calcification of the hydrogel interior. Together with previous studies, these findings suggest that this redox cofactor may play a role in mycobacterial pathogenesis. 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. Bacterial sulfate assimilation pathways provide for activation of inorganic sulfur for the biosynthesis of cysteine and methionine, through either adenosine 5'-phosphosulfate (APS) or 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as intermediates. However, controlled investigations of the relationships between glycosylation, rigidity, and extension of membrane-bound mucins or similar macromolecules are lacking, largely because of the absence of tractable experimental models. 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. View details for Web of Science ID 000173078400005. View details for DOI 10.1371/journal.pone.0242049. View details for Web of Science ID A1992KF46900003, View details for Web of Science ID A1992JB98000009, View details for Web of Science ID A1992HW58200006, View details for Web of Science ID A1992HJ25300046, View details for Web of Science ID A1992HD50000007, View details for Web of Science ID A1991FT18300053, View details for Web of Science ID A1990DE90200028, Baker Family Director, Stanford ChEM-H (2020 - Present), Investigator, Howard Hughes Medical Institute (2000 - Present), Arthur C. Cope Award, American Chemical Society (2017), National Academy of Sciences Award in the Chemical Sciences, National Academy of Sciences (2016), Ernest Orlando Lawrence Award, U.S. Department of Energy (2015), Heinrich Wieland Prize, Heinrich Wieland Prize (2012), Lemelson-MIT Prize, Massachusetts Institute of Technology (2010), Ernst Schering Prize, Ernst Schering Research Foundation (2007), Distinguished Teaching Award, UC Berkeley College of Chemistry (2001), Award in Pure Chemistry, American Chemical Society (2001), MacArthur Foundation Genius Award, MacArthur Foundation (1999), Arthur C. Cope Scholar Award, American Chemical Society (1999), Honorary Degree, Freie University Berlin (2014), Honorary Doctorate Degree, Duke University (2014), Hans Bloemendal Award, Radboud Univ. Peptidoglycan (PG) is an essential component of the bacterial cell wall. This genetically encoded 'aldehyde tag' is no larger than a His(6) tag and can be exploited for numerous protein labeling applications. A cell metabolic labeling experiment can be completed in approximately 4 d. View details for DOI 10.1038/nprot.2007.422, View details for Web of Science ID 000253140000033. 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. Living cells functionalized with exogenous cell-surface DNA strands bind to cognate sequences of DNA printed on glass slides. The controlled addition of structurally defined components to live cell membranes can facilitate the molecular level analysis of cell surface phenomena. Tsai, C., Mukai, K., Robinson, P. V., Gray, M. A., Waschmann, M. B., Lyu, S., Tsai, M., Chinthrajah, R. S., Nadeau, K. C., Bertozzi, C. R., Galli, S. J. Site-specific incorporation of quadricyclane into a protein and photocleavage of the quadricyclane ligation adduct. Using this approach, we identify 133 N-glycosites spanning 58 proteins, nearly doubling the number of experimentally observed N-glycosites in the yeast proteome. 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. Pluvinage, J. V., Haney, M. S., Smith, B. Mucin-domain glycoproteins are known to be key players in a host of human diseases, especially cancer, wherein mucin expression and glycosylation patterns are altered. This human parasite has its own enzymatic machinery for the selective covalent of... Also present a rich matrix of information that adapts rapidly to changing environs these observations suggest crosstalk between autophagy phagocytosis... To the innate immune response of macrophages PMC4567249, View details for DOI 10.1074/mcp.M111.015339, View details for Web Science! 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