Recognized for its roles in membrane tethering, cellular signaling, and protein trafficking, palmitoylation is also emerging as a potential regulator of metabolism. N-Propanoylmannosamine (ManProp), which differs from ManBut by a single methylene group, did not inhibit PSA biosynthesis. View details for DOI 10.1073/pnas.1114356109, View details for Web of Science ID 000302164200031, View details for PubMedCentralID PMC3323966. View details for Web of Science ID 000237590400012. While many GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. View details for DOI 10.1073/pnas.0900717106, View details for Web of Science ID 000264522600009, View details for PubMedCentralID PMC2660766. An N-azidoacetylmannosamine derivative caged with a peptide substrate for the prostate-specific antigen (PSA) protease was converted to cell-surface azido sialic acids in a PSA-dependent manner. [39], In 2014, she co-founded Enable Biosciences[27] of South San Francisco, California. Shui, W., Gilmore, S. A., Sheu, L., Liu, J., Keasling, J. D., Bertozzi, C. R. Synthesis, Characterization, and Theory of [9]-, [12]-, and [18]Cycloparaphenylene: Carbon Nanohoop Structures. When evaluating mouse thymocytes and splenocytes as acceptors of the azido-sugar, a complex pattern of efficiently tagged glycoproteins was revealed. [9] View details for Web of Science ID 000264791600009, View details for PubMedCentralID PMC2657038. Prescher, J. [reaction: see text]. 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. She coined the term bioorthogonal chemistry to describe the use of click reactionsquick, simple chemical reactions to study living cells. In the past decade advances in genomics, proteomics and mass spectrometry have enabled the association of specific glycan structures with disease states. Swarts, B. M., Holsclaw, C. M., Jewett, J. C., Alber, M., Fox, D. M., Siegrist, M. S., Leary, J. Mechanistic and theoretical studies inspired the design of a series of cyclooctyne compounds bearing fluorine substituents, fused rings, and judiciously situated heteroatoms, with the goals of optimizing azide cycloaddition kinetics, stability, solubility, and pharmacokinetic properties. The preferred substrates and functions of the >20 isoforms in mammals are not well understood. The molecular analysis of glycoconjugate function has benefited tremendously from new methods for their chemical synthesis, which provides homogeneous material not attainable from biosynthetic systems. This story was updated on Wednesday, Oct. 6, at 1:23 p.m. PDT. Glycans also present a rich matrix of information that adapts rapidly to changing environs. Assimilatory 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductases are evolutionarily related, homologous enzymes that catalyze the same overall reaction, but do so in the absence of an [Fe-S] cluster. Imbert, P. R., Saric, A. n., Pedram, K. n., Bertozzi, C. R., Grinstein, S. n., Freeman, S. A. Electron-Based Dissociation Is Needed for O-Glycopeptides Derived from OpeRATOR Proteolysis. A correlation between hypersialylation and immunoprotection has been observed, but few hypotheses have provided a mechanistic understanding of this immunosuppressive phenomenon. ( Bertozzi Likewise, branching from the linear chain reduced metabolic conversion. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but the role of mucins in oncogenesis remains poorly understood. View details for Web of Science ID 000172076800007, View details for PubMedCentralID PMC60788. Circumventing the steps of purification from native cell membranes, this methodology facilitates the reconstitution of membrane-associated proteins. The results were in excellent agreement with those obtained from previous assays, verifying the accuracy and reliability of the ESI-MS assay. View details for DOI 10.1074/mcp.M111.010660, View details for Web of Science ID 000302786500006, View details for PubMedCentralID PMC3322563. Chang, P. V., Prescher, J. Changes in glycosylation are often associated with disease progression, but the genetic and metabolic basis of these events is rarely understood in detail at a molecular level. Conceptual translation of the cDNA sequence reveals a relatively long (i.e. Promote and support the Department of Chemistry. Lee, J. H., Baker, T. J., Mahal, L. K., Zabner, J., Bertozzi, C. R., WIEMER, D. F., Welsh, M. J. Exploiting differences in sialoside expression for selective targeting of MRI contrast reagents. These clusters undergo a phase transition through S-layer folding into crystalline clusters composed of compact tetramers. WebPrincipal Investigator. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Sulfolipid-1 (SL-1) is an abundant sulfated glycolipid and potential virulence factor found in Mycobacterium tuberculosis. These synthetic targets incorporate a selectively protected serine residue at the reducing terminus, providing a functional handle for further conjugation. Empty chamber samples were collected between patients as controls.The optimised RASC-2 protocol sampled a median of 258.4L (IQR: 226.9-273.6) of exhaled air per patient compared with 27.5L (IQR: 23.6-30.3) for RASC-1 (p<0.0001). She later refined the approach to improve its utility in cellular environments, facilitating research into interactions between biomolecules and into disease processes. 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. Using these probes, chemoselective imaging of either H(2)O(2) or caspase 8 activity was performed in vitro and in vivo. However, the estimated barrier is much smaller than expected for folding of isolated S-layer proteins, suggesting an energetic rationale for this multistage pathway. The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as one of the key virulence factors of Mycobacterium tuberculosis. This genetically encoded 'aldehyde tag' is no larger than a His(6) tag and can be exploited for numerous protein labeling applications. Antigen presentation to Tcells in major histocompatibility complex class II (MHC class II) requires the conversion of early endo/phagosomes into lysosomes by a process called maturation. Complete assignment of all (1)H and (13)C resonances in the spectra of these deoxytrehaloses was achieved through the extensive use of 2D [(1)H,(1)H] and [(1)H,(13)C] correlation NMR experiments. In addition, the general assay architecture should be readily applicable to high-throughput screens of other carbohydrate sulfotransferases. This system provides a unique framework with which to study the behavior of mucin-like macromolecules in a controlled, cell surface-mimetic environment. The apparent rate constants for the hydrolysis and disappearance of the cell surface conjugates were determined, as well as the apparent rate constant for the formation of covalent bonds with cell surface ketones. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a highly evolved human pathogen characterized by its formidable cell wall. View details for DOI 10.1016/j.cell.2006.08.017, View details for Web of Science ID 000240675000013. First, we found that the W37I mutant of LplA catalyzes site-specific ligation of 10-azidodecanoic acid to LAP in cells, in nearly quantitative yield after 30 min. 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. A., Bertozzi, C. R. Cell type-selective secretome profiling in vivo. Cook, B. N., Bhakta, S., Biegel, T., Bowman, K. G., Armstrong, J. I., Hemmerich, S., Bertozzi, C. R. A "traceless" Staudinger ligation for the chemoselective synthesis of amide bonds. Dr. Bertozzi completed her undergraduate degree in Chemistry at Harvard University and her Ph.D. at A 56-member glycopeptide library designed to reflect a diversity of glycan clustering was assayed for substrate activity with ppGalNAcT isoforms using an azido-ELISA. A Fourier transform ion cyclotron resonance mass spectrometer provided accurate mass measurements, and a quadrupole time-of-flight instrument was used to obtain characteristic fragment ions and partial carbohydrate sequences. Studies showed that a bulky glycocalyx potentiates integrin mechanosignalling and tissue tension and promotes a mesenchymal, stem-like phenotype in GBMs. Hemmerich, S., Bertozzi, C. R., Leffler, H., ROSEN, S. D. FLUORESCENCE PROBES IN BIOCHEMISTRY - AN EXAMINATION OF THE NONFLUORESCENT BEHAVIOR OF DANSYLAMIDE BY PHOTOACOUSTIC CALORIMETRY. View details for DOI 10.1073/pnas.2012196117. Bertozzi shared the 2022 Nobel Prize in Chemistry with two other scientists: Professor Morten Meldal and Professor K Barry Sharpless. A., Bassik, M. C., Moerner, W. E., Bertozzi, C. R. Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis patient bioaerosols. The utility of this approach is demonstrated through the observation of patterned cells as they communicate by diffusion-based paracrine signaling. GPI-anchored proteins play vital roles in signal transduction, the vertebrate immune response, and the pathobiology of trypanosomal parasites. We used this technique to image fucosylated glycans in the enveloping layer of zebrafish embryos during the first 5 days of development. Please refer to the appropriate style manual or other sources if you have any questions. Furthermore, we determined that the PAT biosynthetic machinery has no cross-talk with that for sulfolipid-1 despite their related structures. High mannose glycans are not commonly presented on the surfaces of mammalian cells or in serum yet may play important roles in stem cell biology. Baker Family Director of Stanford ChEM-H, Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences and Professor, by courtesy, of Chemical and Systems Biology and of Radiology, AB, Harvard University, Chemistry (1988). Thus, choice of enrichment strategy has profoundimplications on experimental outcomes. The accumulation of an SL-1 precursor, termed SL(1278), in mmpL8 mutant cells indicates that MmpL8 is necessary for an intermediate step in the SL-1 biosynthesis pathway. These multivalent arrays are 4 orders of magnitude better than the monovalent carbohydrate. Cell surface trehalose mycolates are important modulators of mycobacterial pathogenesis and host immune response. A., Bertozzi, C. R., Marahiel, M. A., Burkart, M. D. Uridine-Based Inhibitors as New Leads for Antibiotics Targeting Escherichia coli LpxC. Using these probes, we studied the mobilities of labeled glycolipids by time-lapse microscopy and fluorescence recovery after photobleaching experiments and found that mycomembrane fluidity varies widely across species and correlates with mycolic acid structure. 135 amino acids) stem region and the presence of several important sequence motifs. View details for DOI 10.1021/acsomega.0c00071, View details for PubMedCentralID PMC7114878. Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. We report that cell surface PSA expression can be reversibly inhibited by a small molecule, N-butanoylmannosamine (ManBut). Oligosaccharides transact information exchange at the cell surface and modulate the activities and distribution of proteins within cells. Liposomes displaying 3'-sulfo Lewis(X)-like oligosaccharides, on the other hand, show slight loss of binding with introduction of additional anionic functional groups for E- and P-selectin and negligible change for L-selectin. View details for DOI 10.1021/acsinfecdis.6b00106, View details for Web of Science ID 000388161300007. Drake, P. M., Stock, C. M., Nathan, J. K., Gip, P., Golden, K. P., Weinhold, B., Gerardy-Schahn, R., Bertozzi, C. R. Selective Enrichment of Azide-Containing Peptides from Complex Mixtures. The resulting trehalose biosynthesis mutant was unable to proliferate and enter stationary phase unless supplemented with trehalose. 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. She has been awarded the Lemelson-MIT Prize, the Heinrich Wieland Prize, and a MacArthur Foundation Fellowship, among many others. Sulfonucleotide reductases are a diverse family of enzymes that catalyze the first committed step of reductive sulfur assimilation. Cell surface reactions of this kind should prove useful in the introduction of new recognition epitopes, such as peptides, oligosaccharides, or small organic molecules, onto cell surfaces and in the subsequent modulation of cell-cell or cell-small molecule binding events. View details for Web of Science ID 000338992200029. Her efforts in undergraduate education have earned her the UC Berkeley Distinguished Teaching Award and the Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching. Fusion of these domains to the proteins FRB and FKBP enabled their induced assembly by the natural product rapamycin. Here we introduce a Pictet-Spengler ligation that is based on the classic Pictet-Spengler reaction of aldehydes and tryptamine nucleophiles. Rodriguez, E. C., Winans, K. A., King, D. S., Bertozzi, C. R. Engineered cell surfaces: Fertile ground for molecular landscaping, Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. This sensitive assay quantifies specific bacteria in a sample without the need to immobilize them or wash away unbound magnetic particles. Phone: (650) 721-4781. Here we demonstrate that the Staudinger ligation can be executed in living animals, enabling the chemical modification of cells within their native environment. 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