Noncovalent complexes of the holoprotein with several ligands, including APS, thioredoxin, and AMP, were also investigated. Cambier, C. J., Banik, S. M., Buonomo, J. Inactivation of the conserved steAB genes (cgp_1603-1604) was also found to confer EMB hypersensitivity and cell division defects. ( Bertozzi We fed cells an unnatural monosaccharide, a modified mannosamine that replaced the acetyl group with a levulinate group (ManLev). In contrast, particles bound to L. monocytogenes are effectively immobilized and relax in about 1 s by rotation of the internal dipole moment. 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. Although the mechanisms of Golgi enzyme localisation are still under debate, the distribution of these enzymes among the Golgi cisternae can dictate the overall structures produced by the cell. View details for Web of Science ID 000088039800042. View details for Web of Science ID 000301161600025, View details for PubMedCentralID PMC3306817. The high signal-to-background ratio obtained using nanomolar concentrations of BARAC obviated the need for washing steps. Heineken Prize for Biochemistry and Biophysics (2022); Wolf Prize (2022); AAAS Lifetime Mentor Award (2022); Presidents Innovator Award, Society for Glycobiology (2020); Nagoya Medal (2020); The Chemistry of the Future Solvay Prize (2020); NAS John J. Carty Award (2020); Glenn T. Seaborg Medal, UCLA (2020); F.A. Under these conditions, Nrf1 is inactive in regulating proteasome subunit gene expression in response to proteasome inhibition. [19][39] Redwood Bioscience was acquired by Catalent Pharma Solutions in 2014. Here we present the design, preparation, and characterization of self-assembling functional bolaamphiphilic polydiacetylenes (BPDAs) inspired by nature's strategy for membrane stabilization. Mougous, J. D., Senaratne, R. H., Petzold, C. J., Jain, M., Lee, D. H., Schelle, M. W., Leavell, M. D., Cox, J. S., Leary, J. The lack of efficient tools meant that it took four years to get a grip on how the glycan functioned. (2001) Glycobiology 11, 11R-18R]. These studies indicate that copper-free crosslinking substrates uniquely offer a diagnostic probe for protein-protein interactions. [85] Her father was of Italian descent. The synthesis of these trehalose analogs sets the stage for future biochemical and NMR-based studies to probe the substrate interactions of trehalose with the recently identified mycobacterial sulfotransferase Stf0. These technological hurdles are especially troublesome in detecting antibodies that bind nonlinear or conformational epitopes, such as anti-insulin antibodies in type 1 diabetes patients and anti-thyroglobulin antibodies associated with thyroid cancers. Metabolic and bioorthogonal labeling methods have previously enabled the enrichment and identification of sialoglycoproteins from cultured cells and model organisms. [92] She has a wife and three sons.[93]. The contributions of cell surface oligosaccharides to critical biological processes such as leukocyte-endothelial cell adhesion, bacterial and viral infection, and immunological recognition of tumor cells and foreign tissue are now understood in significant molecular detail. A., Quang, C. N., Bertozzi, C. R. A sulfated metabolite produced by stf3 negatively regulates the virulence of Mycobacterium tuberculosis. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events. GST-5 has recently been characterized as a novel GalNAc 6-O-sulfotransferase termed chondroitin 6-sulfotransferase-2 (Kitagawa, H., Fujita, M., Itio, N., and Sugahara K. (2000) J. Biol. Photoacoustic calorimetry is shown to be a simple, precise, and accurate method for the quantification of the photophysics of a fluorescence probe, e.g., dansylamide, in a variety of solvents. Lastly, we show that sialic acid depletion enhances ADC lysosomal delivery and killing in diverse cancer cell types, including with FDA (US Food and Drug Administration)-approved trastuzumab emtansine (T-DM1) in Her2-positive breast cancer cells. We demonstrate that gna1Delta strains require a GlcNAc supplement and that expression plasmids containing both exogenous components of the salvage pathway, GlcNAc transporter NGT1 from Candida albicans and GlcNAc kinase NAGK from Homo sapiens, are required for rescue in this context. The competitive inhibitors 2-bromopalmitate and 2-hydroxymyristate prevented incorporation of omega-alkynyl-palmitate and omega-alkynyl-myristate into palmitoylated and myristoylated proteins, respectively. Complementation of the mutant strain restored PAT production, demonstrating that PapA3 is essential for the biosynthesis of this glycolipid in vivo. Schump, M. D., Fox, D. M., Bertozzi, C. R., Riley, L. W. Development of IsoTaG, a Chemical Glycoproteomics Technique for Profiling Intact N- and O-Glycopeptides from Whole Cell Proteomes. Carolyn Bertozzi Hometown: Palo Alto, California Education: AB, Harvard University, 1988; PhD, University of California, Berkeley, 1993 Current position: Director, Stanford Chemistry, Engineering, and Medicine for Human Health; professor of chemistry, Stanford University; and investigator, Howard Hughes Medical Institute The properties of therapeutic proteins can be enhanced by chemical modification. The sulfate assimilation pathway of Mtb produces a number of sulfur-containing metabolites with important contributions to pathogenesis and survival. Mycobacterial carbohydrate sulfotransferase Stf0 catalyzes the sulfuryl group transfer from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to trehalose. Thus, BARAC is a promising reagent for in vivo imaging. Palaniappan, K. K., Hangauer, M. J., Smith, T. J., Smart, B. P., Pitcher, A. Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified protein in the outer leaflet of the cell membrane. Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. [9] Although theoretical predictions suggest that proteins follow these pathways as a result of fluctuations that create unstable dense-liquid states, microscopic studies indicate these states are long-lived. She is the 50th American Cancer Society -funded researcher and the first woman researcher funded by ACS to win the prestigious honor. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Kinetic analysis of the mutants identified residues that are essential for catalytic activity. Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. The azidofluorescein derivative also enabled cell imaging under no-wash conditions with good signal above background. We designed synthetically tractable glycosylated polymers that possess rodlike extended conformations similar to natural mucins. We found that N-azidoacetylgalactosamine (GalNAz) is converted by endogenous mammalian biosynthetic enzymes to UDP-GalNAz and then epimerized to UDP-N-azidoacetylglucosamine (GlcNAz). 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. We identified and characterized a conserved mycobacterial sulfotransferase, Stf0, which generates the T2S moiety of SL-1. Mycobacterium tuberculosis ( Mtb) produces a number of sulfur-containing metabolites that contribute to its pathogenesis and ability to survive in the host. This system thus constitutes an AND-type molecular logic gate that reports on the simultaneous presence of H(2)O(2) and caspase 8 activity. We report herein the chemical synthesis and preliminary mechanistic investigation of diptericin, an 82 residue glycopeptide that contains regions similar to two different types of antibacterial peptides. Chen, X., Lee, G. S., Zettl, A., Bertozzi, C. R. Functional glass slides for in vitro evaluation of interactions between osteosarcoma TE85 cells and mineral-binding ligands. We functionalized cells with short oligonucleotides to impart specific adhesive properties. The versatility of this technology was demonstrated by an example of selective drug delivery. Finally, mechanistic and structural data from sulfate-assimilation enzymes have revealed how M. tb controls the flux of sulfate in the cell. ScTyrY43G and MmPheT413G label overlapping but distinct proteomes in human cell lines, with broader proteome coverage upon their coexpression. 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. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. This process involves two steps. Lipid-derived desiccation resistance in membranes is a rare, unique ability previously observed only with trehalose dimycolate (TDM), an abundant mycobacterial glycolipid. A sensitive electrospray ionization mass spectrometry-based assay was used to extract the kinetic parameters for PAP, revealing a K m (8.1 +/- 3.1 microM) and k cat (5.4 +/- 1.1 s (-1)) comparable to those reported for other CysQ enzymes. To establish this approach, we have developed Peroxy Caged Luciferin-2 (PCL-2), a H(2)O(2)-responsive boronic acid probe that releases 6-hydroxy-2-cyanobenzothiazole (HCBT) upon reacting with this reactive oxygen species, as well as a peptide-based probe, z-Ile-Glu-ThrAsp-D-Cys (IETDC), which releases D-cysteine in the presence of active caspase 8. View details for DOI 10.1073/pnas.0809218105, View details for Web of Science ID 000260913800030, View details for PubMedCentralID PMC2579359. Walton, E. M., Cronan, M. R., Cambier, C. J., Rossi, A., Marass, M., Foglia, M. D., Brewer, W., Poss, K. D., Stainier, D. R., Bertozzi, C. R., Tobin, D. M. A tension-mediated glycocalyx-integrin feedback loop promotes mesenchymal-like glioblastoma. Additionally, it is helpful if one reactive group is small and therefore minimally perturbing of a biomolecule into which it has been introduced either chemically or biosynthetically. IsoTaG is therefore an effective platform for identification of intact glycopeptides labeled by alkynyl or azido sugars and will facilitate further studies of the glycoproteome. View details for DOI 10.1073/pnas.0700567104, View details for Web of Science ID 000246599900007, View details for PubMedCentralID PMC1895932. Wei, W., Riley, N. M., Lyu, X., Bertozzi, C. R., Long, J. She is known for creating the term "bioorthogonal chemistry" for chemical reactions with living systems. This strategy requires no chemical modification of the N-glycans or stringent sample enrichment. We combined CRISPR-Cas9 knockout screens with RNAsequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. Sulfated constituents of GlyCAM-1 were identified as Gal-6-SO4, GlcNAc-6-SO4, (SO4-6)Gal beta 1-->4GlcNAc, and Gal beta 1-->4(SO4-6)GlcNAc. of Chemistry (2018); Foreign Member of the Royal Society Inductee (2018); National Inventors Hall of Fame Inductee (2017); Arthur C. Cope Award (2017); UCSF 150th Anniversary Alumni Excellence Award (2015); Hans Bloemendal Award (Radboud Univ. Illumination of dye-labeled structures generates singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product that is readily imaged by EM. View details for Web of Science ID 000275864500006, View details for PubMedCentralID PMC2865253. Therefore, sulfation may increase the estrogenic potential of xenobiotics. Azido sugars are fed to cells or organisms and integrated by the glycan biosynthetic machinery into various glycoconjugates. 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. Although the polysialyltransferase ST8Sia IV is expressed in both primary and secondary human lymphoid organs, its product, polysialic acid (polySia), has been largely overlooked by immunologists. Winans, K. A., King, D. S., Rao, V. R., Bertozzi, C. R. Engineering novel cell surface receptors for virus-mediated gene transfer. Li phin vn-chng si to pan-lan-chhan , ng cho-tet yung phin-si fet-ch khok-chhng kh ke nui-yng. The d-alanine analogues were specifically incorporated into nascent PG of the intracellular pathogen Listeria monocytogenes both in vitro and during macrophage infection. The widespread role of sulfotransferases in modulating glycan function makes them prime targets for small-molecule modulators. Li phin vn-chng si to pan-lan-chhan , ng 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. View details for Web of Science ID 000294081900008. Multiple Ygp1 N-glycosylation sites bearing GlcNAc, isotopically labeled GlcNAc, or GlcNAz were identified; these modifications were dependent on the supplement added to the culture medium. At elevated temperatures, however, the mutant was unable to proliferate even in the presence of trehalose. We previously established that mouse multipotent hematopoietic progenitors use ST8Sia IV to express polySia on their cell surfaces. Glycans can be imaged by metabolic labeling with azidosugars followed by chemical reaction with imaging probes; however, tissue-specific labeling is difficult to achieve. View details for DOI 10.1002/anie.200806319, View details for Web of Science ID 000266415400022, View details for PubMedCentralID PMC2868584. Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7. View details for DOI 10.1073/pnas.0307128101, View details for Web of Science ID 000187937200026, View details for PubMedCentralID PMC314150, View details for DOI 10.1002/anie.200352673, View details for Web of Science ID 000220266000010, View details for DOI 10.1002/anie.200454235, View details for Web of Science ID 000224592400009, View details for DOI 10.1002/anie.200460620, View details for Web of Science ID 000225445200005, View details for Web of Science ID 000223490500010. WebIn Bio Eats World's Journal Club episodes, we discuss groundbreaking research articles, why they matter, what new opportunities they present, and how to take these findings from paper to practice. 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. Here, we compared these chemistries in the context of various biological applications, including labeling of biomolecules in complex lysates and on live cell surfaces. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" These mutations activated the JAK-STAT signaling pathway and conferred sensitivity to JAK inhibitors. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate. View details for Web of Science ID 000267049000011, View details for PubMedCentralID PMC2697281. View details for Web of Science ID 000077136900049, View details for Web of Science ID 000076649700013, View details for Web of Science ID 000075884200020. Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. Malaker, S. A., Shon, J., Pedram, K., Riley, N. M., Bertozzi, C. R. AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. An RNA-centric dissection of host complexes controlling flavivirus infection. Expansion of this toolkit, an effort that is already well underway, is an important objective for chemists and biologists alike. View details for Web of Science ID 000264791600009, View details for PubMedCentralID PMC2657038. 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. Azide-labeled proteins are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization. A., Shrager, J. Bioorthogonal tools enable cell-type-specific proteomics, a prerequisite to understanding biological processes in multicellular organisms. Disruption of the papA3 gene from M. tuberculosis resulted in the loss of PAT from bacterial lipid extracts. For the glycopeptide substrates, ppGalNAc T10 exhibited a single large preference for Ser/Thr-O-GalNAc at the +1 (C-terminal) position relative to the Ser or Thr acceptor site. Cell surface lipooligosaccharides (LOS) of H. ducreyi are thought to play important biological roles in host infection. View details for DOI 10.1146/annurev.biochem.71.110601.135334, View details for Web of Science ID 000177352600021. View details for DOI 10.1126/science.1155106, View details for Web of Science ID 000255454300046. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. In this paper, we describe experiments in which the conformations of structurally well-defined polymers anchored to fluid lipid membranes were probed using Fluorescence Interference Contrast Microscopy (FLIC), an optical technique that provides topographic information with few-nanometer precision. We find that the orientation of the rigid, approximately 30 nm long glycopolymers depends profoundly on the properties of the optical reporter. LC-MS/MS mass spectrometry analysis was then performed and the processed data related to the identified glycoproteins show that several hundred proteins are differentially expressed between control and GALNT3 KD A2780s cells. 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. Cross-linked polymethacrylamide and polymethacrylate hydrogels were functionalized with mineral-binding ligands and used to template the formation of hydroxyapatite. The C-type lectins dectin-1 and dectin-2 contribute to innate immunity against microbial pathogens by recognizing their foreign glycan structures. Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. Recently, the ability to modify monosaccharide structures within cellular glycans through metabolic processes has offered a new avenue for biological studies. Glycocalyx Engineering with a Recycling Glycopolymer that Increases Cell Survival In Vivo. A key feature of the synthesis was application of an intramolecular aglycon delivery reaction to join two differentially protected glucose monomers, one prepared with a novel alpha-selective glycosylation. Shieh, P., Siegrist, M. S., Cullen, A. J., Bertozzi, C. R. Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. The remodeled cells were endowed with novel lectin binding profiles as determined by flow cytometry analysis. View details for Web of Science ID 000182959600044. Although they represent the majority of cell surface sialosides, analogs with longer N-acyl groups diminish the overall level of LOS sialylation, culminating in complete inhibition of LOS sialylation by N-octanoyl sialic acid. This approach should be applicable to any glycosyltransferase or group-transfer enzyme that tolerates unnatural azido substrates. 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. We structurally assigned 32 N-glycopeptides and over 500 intact and fully elaborated O-glycopeptides from 250 proteins across three human cancer cell lines and also discovered unexpected peptide sequence polymorphisms (pSPs). Low molecular weight and singly charged fragments, obtained by a combination of gel filtration and anion-exchange chromatography, were analyzed. In this mechanism, PAPS and trehalose bind and their products are released in random fashion. Using high-performance liquid chromatography, we quantified the degree of accumulation and reversibility upon acidic compartment neutralization in macrophages and observed that accumulation was greater in infected than in uninfected macrophages. Myristoylation is the attachment of the 14-carbon fatty acid myristate to the N-terminal glycine residue of proteins. Woods, E. C., Kai, F., Barnes, J., Pedram, K., Pickup, M. W., Hollander, M. J., Weaver, V. M., Bertozzi, C. R. Exploring the role of Nrf1 in NGly1 deficiency. Here we describe the characterization and application of a synthetic riboswitch-based system, which comprises a mycobacterial promoter for transcriptional control and a riboswitch for translational control. View details for DOI 10.1073/pnas.1608069113. The polymers were designed to mimic native cell-surface mucin glycoproteins, which are defined by their dense glycosylation patterns and rod-like structures. Preliminary screening has identified compounds that inhibit estrogen sulfotransferase (EST), an enzyme relevant to breast cancer. This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes. With this technique, we studied the dynamics of glycan trafficking and identified a population of sialoglycoconjugates with unexpectedly rapid internalization kinetics. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. Chen, X., Kis, A., Zettl, A., Bertozzi, C. R. Hierarchical assembly of model cell surfaces: Synthesis of mucin mimetic polymers and their display on supported bilayers. 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. A novel and efficient enzyme kinetics assay using electrospray ionization mass spectrometry was developed and applied to the bacterial carbohydrate sulfotransferase (NodST). CysQ is a 3'-phosphoadenosine-5'-phosphatase that dephosphorylates intermediates from the sulfate assimilation pathway of Mycobacterium tuberculosis (Mtb). Woo, C. M., Iavarone, A. T., Spiciarich, D. R., Palaniappan, K. K., Bertozzi, C. R. The cancer glycocalyx mechanically primes integrin-mediated growth and survival. View details for DOI 10.1371/journal.pone.0065080, View details for Web of Science ID 000321099000031, View details for PubMedCentralID PMC3675115. Abnormalities in the synthesis or presentation of these carbohydrates can lead to misfolded and inactive proteins, as well as to several debilitating disease states. Here, a sequence-based analysis of newly discovered mycobacterial sulfotransferase genes, named stf1-stf10, is presented. Converse, S. E., Mougous, J. D., Leavell, M. D., Leary, J. [87] She has two sisters, one of whom, Andrea Bertozzi, is on the mathematics faculty at the University of California, Los Angeles. Assays based on solid-phase immobilization of antigens comprise the majority of clinical platforms for antibody detection, but can be undermined by antigen denaturation and epitope masking. View details for DOI 10.1021/jacs.0c07700. The rapid assembly of a complex type N-linked glycopeptide mimetic was accomplished using this technique. A., Ogorzalek Loo, R. R., Lundberg, E. n., MacCoss, M. J., Mallick, P. n., Mootha, V. K., Mrksich, M. n., Muir, T. W., Patrie, S. M., Pesavento, J. J., Pitteri, S. J., Rodriguez, H. n., Saghatelian, A. n., Sandoval, W. n., Schlter, H. n., Sechi, S. n., Slavoff, S. A., Smith, L. M., Snyder, M. P., Thomas, P. M., Uhln, M. n., Van Eyk, J. E., Vidal, M. n., Walt, D. R., White, F. M., Williams, E. R., Wohlschlager, T. n., Wysocki, V. H., Yates, N. A., Young, N. L., Zhang, B. n. Mapping and quantification of over 2,000 O-linked glycopeptides in activated human T cells with isotope-targeted glycoproteomics (IsoTaG). We report here a study of mycomembrane dynamics that was enabled by trehalose-fluorophore conjugates capable of labeling trehalose glycolipids in live actinomycetes. The azide was detected and quantified by Staudinger ligation with a phosphine probe in a microtiter plate format. Cohen, A. S., Dubikovskaya, E. A., Rush, J. S., Bertozzi, C. R. Visualizing enveloping layer glycans during zebrafish early embryogenesis. We used these tools to perform the first site-directed mutagenesis study of a member of this sulfotransferase family, GST2. Both biochemical and structural data indicate the presence of an oxidized cysteine modification in the active site that may be relevant to catalysis. Metabolic labeling of glycans with a bioorthogonal chemical reporter such as the azide enables their visualization in cells and organisms as well as the enrichment of specific glycoprotein types for proteomic analysis. To differentiate sulfated from reduced-sulfur-containing molecules, we employed a mutant lacking the reductive branch of the sulfate assimilation pathway. In this reaction, activated sulfate in the context of adenosine-5'-phosphosulfate (APS) or 3'-phosphoadenosine 5'-phosphosulfate (PAPS) is converted to sulfite with reducing equivalents from thioredoxin. WebCarolyn Bertozzi, PhD. 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. Ganesan, L., Shieh, P., Bertozzi, C. R., Levental, I. Isotope-targeted glycoproteomics (IsoTaG) analysis of sialylated N- and O-glycopeptides on an Orbitrap Fusion Tribrid using azido and alkynyl sugars. Presented herein is the synthesis and evaluation of a bisubstrate analogue designed to inhibit estrogen sulfotransferase. A combination of expressed protein ligation and native chemical ligation was used to attach these analogues to the green fluorescent protein (GFP). View details for DOI 10.1002/anie.201508861, View details for Web of Science ID 000368061800024, View details for PubMedCentralID PMC4715665. Hudak, J. E., Barfield, R. M., de Hart, G. W., Grob, P., Nogales, E., Bertozzi, C. R., Rabuka, D. Synthesis of a Fluorogenic Cyclooctyne Activated by Cu-Free Click Chemistry, Protein Glycoengineering Enabled by the Versatile Synthesis of Aminooxy Glycans and the Genetically Encoded Aldehyde Tag, Cell surface glycoproteomic analysis of prostate cancer-derived PC-3 cells. View details for Web of Science ID 000187945400003. Analysis of the genomes of M. tuberculosis, M. leprae, M. smegmatis, and M. avium has revealed a large family of genes homologous to known sulfotransferases. Moreover, concomitant use of PCL-2 and IETDC in vivo establishes a concurrent increase in both H(2)O(2) and caspase 8 activity during acute inflammation in living mice. This assay is 1,000-10,000 times more analytically sensitive than clinical enzyme-linked immunoassays (EIAs), displaying both 100% clinical sensitivity and 100% specificity for detecting HIV antibodies within OF samples. 56Carolyn Bertozzi 12 Bertozzi won the prize for studying the sugar coats of cells. Agarwal, P., van der Weijden, J., Sletten, E. M., Rabuka, D., Bertozzi, C. R. Real-Time Noninvasive Imaging of Fatty Acid Uptake in Vivo. In the mouse genome we have found a homologous ORF that predicts a novel murine GlcNAc 6-O-sulfotransferase with 88% identity to the human enzyme. WebAbout our Founding. The importance of sulfated molecules in cell-cell communication motivated us to develop a rapid two-step method for identifying these metabolites in microorganisms, particularly in pathogenic mycobacteria. Mycobacterium tuberculosis and Mycobacterium smegmatis possess three pathways for the synthesis of trehalose. Our results demonstrate a key role of PIKfyve in the processing and presentation of antigens, which should be taken into consideration when targeting PIKfyve in autoimmune disease and cancer. 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.