The increase of cell surface sialic acid is a characteristic shared by many tumor types. This gene was mapped to mouse chromosome X at band XA3.1-3.2. Bertozzi completed her undergraduate degree in Chemistry at Harvard University and her Ph.D. at UC Berkeley, focusing on the chemical synthesis of oligosaccharide analogs. [27][41], Bertozzi became a co-founder of Palleon Pharma of Waltham, Massachusetts, in 2015. Cyclopropanation of the mycobacterial cell wall glycolipid trehalose dimycolate is both required and sufficient to induce robust host angiogenesis. ( Bertozzi They also suggest increased P. aeruginosa adhesion to MyD88-/- and blotted corneas is not due to reduction in total surface glycosylation, and for tissue paper blotting is likely due to cell permeabilization.-Jolly, A. L., Agarwal, P., Metruccio, M. M. E., Spiciarich, D. R., Evans, D. J., Bertozzi, C. R., Fleiszig, S. M. J. Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding. Wu, P., Shui, W., Carlson, B. L., Hu, N., Rabuka, D., Lee, J., Bertozzi, C. R. Boron Nitride Nanotubes Are Noncytotoxic and Can Be Functionalized for Interaction with Proteins and Cells. Belardi, B., de la Zerda, A., Spiciarich, D. R., Maund, S. L., Peehl, D. M., Bertozzi, C. R. A Chemical Glycoproteomics Platform Reveals O-GlcNAcylation of Mitochondrial Voltage-Dependent Anion Channel 2. In the first step of the pathway, APS reductase catalyzes the reduction of adenosine 5'-phosphosulfate (APS) to adenosine 5'-phosphate (AMP) and sulfite with reducing equivalents from the protein cofactor, thioredoxin. Mahal, L. K., Yarema, K. J., Bertozzi, C. R. An ELISA for selectins based on binding to a physiological ligand. Screening of a saturation mutagenesis library of the E. coli methionyl-tRNA synthetase (MetRS) led to the discovery of three MetRS mutants capable of incorporating the long-chain amino acid azidonorleucine into recombinant proteins with modest efficiency. To determine whether PapA3 participates in PAT assembly, we expressed the protein heterologously and evaluated its acyltransferase activity in vitro. View details for Web of Science ID 000177297600001. The end purpose of the described approaches is the production of glycosylated materials for experiments relevant to the biological investigation of glycoproteins, although the strategies presented apply to other posttranslational modifications as well. Even though we have only demonstrated its use in visualizing glycans, it can be envisioned that this probe could also be used for bioluminescence imaging of any azide-containing biomolecule, such as proteins and lipids, since azides have been previously incorporated into these molecules. Molecular imaging with chemical reporters offers a new avenue for probing changes in the glycome that accompany development and disease. Therapeutic strategies that target tumor-associated sialosides may therefore potentiate antitumor immunity. Bertozzi is a professor Beam-type collisional activation, i.e., higher-energy collisional dissociation (HCD), has been a valuable approach, but stepped collision energy HCD (sceHCD) and electron transfer dissociation with HCD supplemental activation (EThcD) have emerged as potentially more suitable alternatives. We demonstrated the method by constructing site-specifically glycosylated variants of the human growth hormone. Numerous factors that influence cell-surface carbohydrate composition remain to be elucidated. Fluorogenic probes activated by bioorthogonal chemical reactions can enable biomolecule imaging in situations where it is not possible to wash away unbound probe. A., Bertozzi, C. R. Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation. These findings provide a platform for defining the molecular basis of SMK's role in M. tuberculosis pathogenesis. 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. Webauthor = "Burrows, {Cynthia J.} The synthetic glycolipids consist of a simple trehalose disaccharide headgroup, similar to TDM, with hydrophobic tail groups of two 15- or 18-carbon chains. Blocking PIKfyve activity by small molecule inhibitors caused a delay in the conversion of phagosomes into lysosomes and in phagosomal acidification, whereas production of reactive oxygen species (ROS) increased. To enable noninvasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). The coating layers of macrophages and their targets hinder phagocytosis by both steric and electrostatic means. A ligation modeled after the Staudinger reaction forms an amide bond by coupling of an azide and a specifically engineered triarylphosphine. Two notable examples are the Staudinger ligation of azides and phosphines and the Cu(I)-catalyzed [3 + 2] cycloaddition of azides and alkynes ("click chemistry"). The ESI-MS assay is used to determine NodST kinetic parameters, including K(M), V(max), and K(i) (for PAP). Herein we analyzed the glycopeptide substrate preferences of several ppGalNAcT family members using a library screening approach. [30] In 2015, Bertozzi moved to Stanford University to join the ChEM-H Institute. Their diffusion properties mirrored those of many natural membrane-associated biomolecules. In addition, GalNAz efficiently labeled mucin-type O-linked glycoproteins expressed at endogenous levels. 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. Furthermore, GalNAz-labeled B cells could be selectively targeted with a phosphine probe by Staudinger ligation within the living animal. After subsequent injection with cyclooctyne reagents, glycoconjugate labeling was observed on isolated splenocytes and in a variety of tissues including the intestines, heart, and liver, with no apparent toxicity. The lipooligosaccharides (LOS) of Haemophilus ducreyi are highly sialylated, a modification that has been implicated in resistance to host defense and in virulence. Carolyn Ruth Bertozzi (born October 10, 1966) is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. Agard, N. J., Prescher, J. We identified a concise disaccharide motif, GlcNAc beta 1-->6Gal alpha-R, that preserved both recognition and specificity determinants for the GlcNAc-6-0-sulfotransferase. Mucin-type O-linked glycosylation is a fundamental post-translational modification that is involved in a variety of important biological processes. Hotsclaw, C. M., Sogi, K. M., Gilmore, S. A., Scheller, M. W., Leavell, M. D., Bertozzi, C. R., Leary, J. A., Lo, A., Codelli, J. The Staudinger ligation with alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents. She grew up in Lexington, Massachusetts with two sisters, one of which is on the mathematics faculty at the University of California, Los Angeles (UCLA). Driessen, M. D., Going, C. C., Woo, C. M., Pitteri, S. J., Bertozzi, C. R. New therapeutic avenues for NGLY1 deficiency, A TENSION-MEDIATED GLYCOCALYX FEEDBACK LOOP PROMOTES A MESENCHYMAL, STEM-LIKE PHENOTYPE IN GLIOBLASTOMA. 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. Therefore, sulfation may increase the estrogenic potential of xenobiotics. [9] The glycan symbol nomenclature proposed by Harvey et al. Sulfate assimilation is a critical component of both primary and secondary metabolism. However, changes in the glycan structure significantly affected membrane mobility, with the loss of monosaccharide units correlating to decreased diffusion. Glycosyltransferases responsible for synthesis of cell surface oligosaccharides are therefore essential administrators of cellular communication. 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. However, because they are internalized within hours, these glycopolymers could not be employed to probe processes that occur on longer time scales. Chemical tools have accelerated progress in glycoscience, reducing experimental barriers to studying protein glycosylation, the most widespread and complex form of posttranslational modification. Saxon, E., Luchansky, S. J., Hang, H. C., Yu, C., Lee, S. C., Bertozzi, C. R. Carbohydrate sulfotransferases of the GalNAc/Gal/GlcNAc6ST family, Kinetic analysis of NodST sulfotransferase using an electrospray ionization mass spectrometry assay. View details for DOI 10.1073/pnas.1010045108, View details for Web of Science ID 000287580400017. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Mockl, L., Pedram, K., Roy, A., Krishnan, V., Gustavsson, A., Dorigo, O., Bertozzi, C., Moerner, W. Enzyme toolkit for selective enrichment and analysis of mucin-domain glycoproteins. The assay is suitable for high-throughout screening of compounds and may find use in the identification of selectin antagonists with anti-inflammatory potential. Though not directly subject to mutation, we can determine glycan structure-function relationships by synthesizing defined glycoconjugates or by altering natural glycosylation pathways. The use of symbols to depict glycans originated from Kornfeld in 1978, was systematized in the First Edition of "Essentials of Glycobiology" and updated for the second edition, with input from relevant organizations such as the Consortium for Functional Glycomics. 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. Here, we tracked the assembly dynamics of different envelope layers in Corynebacterium glutamicum and Mycobacterium smegmatis by using metabolic labeling and found that the septal cell envelope is assembled sequentially in both species. T-cell progenitors originate in the bone marrow and are mobilized to the blood at regular intervals by unknown signals. In particular, Bertozzi has advanced the understanding of cell surface oligosaccharides involved in cell recognition and inter-cellular communication. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a highly evolved human pathogen characterized by its formidable cell wall. Under nondenaturing conditions, a distribution of the apoprotein, a 2Fe-2S intermediate, and the 4Fe-4S holoprotein were observed. Small molecule inhibitors of carbohydrate biosynthetic and processing enzymes can block the assembly of specific oligosaccharide structures. Such structural alterations to cell surface glycans can be used to probe carbohydrate-dependent phenomena. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. View details for DOI 10.1021/jacs.0c07700. A., Bertozzi, C. R. Synthetic Trehalose Glycolipids Confer Desiccation Resistance to Supported Lipid Monolayers. These metabolites are products of the sulfate assimilation pathway. Kinetic studies revealed significant inhibitory activity and provide guidance for improved inhibitor design. 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 DOI 10.1002/cbic.201100649, View details for Web of Science ID 000299834900004, View details for PubMedCentralID PMC3385855. Bacteria are able to adapt to dramatically different microenvironments, but in many organisms, the signaling pathways, transcriptional programs, and downstream physiological changes involved in adaptation are not well-understood. These data provide strong evidence that Stf0 carries out the first committed step in the biosynthesis of SL-1 and establish a system for probing the role of SL-1 in M. tuberculosis infection. A major challenge in fundamental studies of galectin-ligand interactions is that their natural ligands comprise a heterogeneous collection of glycoconjugates that share related glycan structures but disparate underlying scaffolds. Sialylated glycans are found at elevated levels in many types of cancer and have been implicated in disease progression. 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. Breidenbach, M. A., Palaniappan, K. K., Pitcher, A. We devised an experimental model that mimics the structure of mycobacterial envelopes in which an immobile hydrophobic layer supports a TDM-rich, two-dimensionally fluid leaflet. Finally, the Delta papA2 and Delta papA1 mutants were screened for virulence defects in a mouse model of infection. 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