PCL-1 is a boronic acid-caged firefly luciferin molecule that selectively reacts with H(2)O(2) to release firefly luciferin, which triggers a bioluminescent response in the presence of firefly luciferase. View details for DOI 10.1016/j.molcel.2020.03.030. This tutorial review focuses on recent applications of homogeneous synthetic glycopeptides and glycoproteins for studies of structure and function. View details for Web of Science ID 000250260500015. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. We exploited StcE's unique properties to improve sequence coverage, glycosite mapping, and glycoform analysis of recombinant human mucins by mass spectrometry. The Staudinger ligation has sufficient biocompatibility for performance in living animals but suffers from phosphine oxidation and synthetic challenges. Sulfation of GlcNAc within sialyl Lewis x is a crucial modification for L-selectin binding, and thus, the underlying sulfotransferase may be a key modulator of lymphocyte trafficking. We used the reaction for site-specific chemical modification of glyoxyl- and formylglycine-functionalized proteins, including an aldehyde-tagged variant of the therapeutic monoclonal antibody Herceptin. Small molecule inhibitors of carbohydrate biosynthetic and processing enzymes can block the assembly of specific oligosaccharide structures. Cyclopropanation of the mycobacterial cell wall glycolipid trehalose dimycolate is both required and sufficient to induce robust host angiogenesis. Banik, S. M., Pedram, K., Wisnovsky, S., Ahn, G., Riley, N. M., Bertozzi, C. R. Immunoglobulin E sialylation regulates allergic responses. 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. The method was applied to the discovery of several new sulfated molecules in Mycobacterium tuberculosis and Mycobacterium smegmatis. Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7. Hotsclaw, C. M., Sogi, K. M., Gilmore, S. A., Scheller, M. W., Leavell, M. D., Bertozzi, C. R., Leary, J. Site-selective protein modification based on covalent reactions of peptide tags and small molecules is a key capability for basic research as well as for the development of new therapeutic bioconjugates. View details for DOI 10.1016/j.devcel.2019.04.035. Therefore, development of an effective new vaccine has gained momentum in recent years. The availability of this new protocol greatly expands the applicability of the DNA-based attachment strategy for the generation of artificial tissues and the incorporation of living cells into device settings. Wang, S., Gray, M. A., Xuan, S., Lin, Y., Byrnes, J., Nguyen, A. I., Todorova, N., Stevens, M. M., Bertozzi, C. R., Zuckermann, R. N., Gang, O. DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis. The biophysical properties of the system are characterized, and the technique is used to form complex cellular patterns with single-cell line widths and self-assembled cellular microarrays. By controlling the pools of 3'-phosphoadenosine 5'-phosphate (PAP) and 3'-phosphoadenosine 5'-phosphosulfate (PAPS), CysQ has the potential to modulate flux in the biosynthesis of essential sulfur-containing metabolites. We used the CalFluor probes to image various alkyne-labeled biomolecules (glycans, DNA, RNA, and proteins) in cells, developing zebrafish, and mouse brain tissue slices. Issues such as stability of reactants and products (particularly in water), kinetics, and unwanted side reactivity with biofunctionalities must be addressed, ideally guided by detailed mechanistic studies. We engineered tumor cells to display glycocalyces of various thicknesses by coating them with synthetic mucin-mimetic glycopolymers. This represents over a million-fold signal amplification in comparison to using radioactive labeling methods. Here, we use metabolic oligosaccharide engineering to introduce a bioorthogonal functional group, the azide, into cellular and recombinant glycoproteins for subsequent chemical elaboration via Staudinger ligation. Polysialyltransferases catalyze the glycosylation of the neural cell adhesion molecule (NCAM) with polysialic acid (PSA). This Account summarizes chemoselective approaches for assembling homogeneous glycoconjugates that attempt to reduce the barriers to their synthesis. Recently, several M. tuberculosis mutants were tested as potential vaccine candidates in the mouse model of tuberculosis. N610 was also the primary site of sialylation of the receptor. View details for DOI 10.1016/j.jasms.2006.08.010, View details for Web of Science ID 000244109300001, View details for PubMedCentralID PMC2755055. 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. Despite being immunologically distinct, poly(SiaProp) can promote neurite outgrowth similarly to natural polysialic acid. 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. Accurate mass measurements indicated an oxidation state of +2 for the 4Fe-4S cluster, with no disulfide bond in the holoenzyme. The structurally uniform alkyne-terminated mucin mimetic glycopolymers (see picture; TR = fluorophore) were printed on azide-functionalized chips by microcontact printing in the presence of a copper catalyst. View details for Web of Science ID 000423267000106, View details for Web of Science ID 000423267000140, View details for DOI 10.1021/acscentsci.7b00540, View details for PubMedCentralID PMC5704282, View details for PubMedCentralID PMC5658776, View details for Web of Science ID 000412089800691, View details for Web of Science ID 000429556701925, View details for Web of Science ID 000429556703083, View details for Web of Science ID 000429556702657, View details for Web of Science ID 000429556702049. Chemical tools have accelerated progress in glycoscience, reducing experimental barriers to studying protein glycosylation, the most widespread and complex form of posttranslational modification. These results should facilitate mechanistic studies and the development of small molecule inhibitors of this enzyme family to ameliorate chronic inflammatory diseases. Pathogenic bacteria have developed numerous mechanisms to survive inside a hostile host environment. 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. Most cell membrane proteins are known or predicted to be glycosylated in eukaryotic organisms, where surface glycans are essential in many biological processes including cell development and differentiation. Finally, we demonstrate that the cell-surface Staudinger ligation is compatible with hydrazone formation from metabolically introduced ketones. Mycobacteria contain high levels of the disaccharide trehalose in free form as well as within various immunologically relevant glycolipids such as cord factor and sulfolipid-1. A combination of quantitative microscopy, mutational analysis, and interaction studies indicate that SteA and SteB form a complex that localizes to the cytokinetic ring to promote cell separation by RipC-FtsEX and may coordinate its PG remodeling activity with the biogenesis of other envelope layers during cell division. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)-sulfate, that detects enzyme activity in native protein gels, allowing the rapid detection of sulfatases in mycobacterial lysates. In this context, polySia modulates cellular adhesion, migration, cytokine response, and contact-dependent differentiation. 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. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Two approaches that emphasize developing selective methods to dissect, modify, and control receptor-ligand interactions at the cellular interface are discussed. Parak, W. J., Gerion, D., Zanchet, D., Woerz, A. S., Pellegrino, T., Micheel, C., Williams, S. C., Seitz, M., Bruehl, R. E., Bryant, Z., Bustamante, C., Bertozzi, C. R., Alivisatos, A. P. Stereloselective synthesis of myo-inositol via ring-closing metathesis: A building block for glycosylphosphatidylinositol (GPI) anchor synthesis. Increased levels of circulating saturated free fatty acids, such as palmitate, have been implicated in the etiology of type II diabetes and cancer. The ability to generate chemically defined analogues of GPI-anchored proteins is an important step toward elucidating the molecular functions of this interesting post-translational modification. Hsiao, S. C., Crow, A. K., Lam, W. A., Bertozzi, C. R., Fletcher, D. A., Francis, M. B. Chemical reactions that enable selective biomolecule labeling in living organisms offer a means to probe biological processes in vivo. Detection of metabolites and post-translational modifications can be achieved using the azide as a bioorthogonal chemical reporter. O-Linked -N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome. The expanding integrin wave facilitates the zippering of Fc receptors onto the target and integrates the information from sparse receptor-ligand complexes, coordinating the progression and ultimate closure of the phagocytic cup. (1994) Biochemistry 33, 4830-4835] evidence is presented that (SO4-6)Gal beta 1-->4GlcNAc forms the core of a sulfated sialyl Lewis x structure that may comprise a recognition determinant on GlyCAM-1. Preliminary screening has identified compounds that inhibit estrogen sulfotransferase (EST), an enzyme relevant to breast cancer. Binda, O., Boyce, M., Rush, J. S., Palaniappan, K. K., Bertozzi, C. R., Gozani, O. Organelle Membrane Proteomics Reveals Differential Influence of Mycobacterial Lipoglycans on Macrophage Phagosome Maturation and Autophagosome Accumulation. A library of potential bisubstrate analogue inhibitors (1) targeting sulfotransferase enzymes was generated by the chemoselective ligation of the PAPS mimic 2 with a panel of 447 aldehydes. View details for Web of Science ID 000082757300015. We demonstrated that these catalytically inactive point mutants enable robust detection and visualization of mucin-domain glycoproteins by flow cytometry, Western blot, and immunohistochemistry. Paulk, N. K., Rumachik, N., Malaker, S., Adams, C., Leib, R., Bertozzi, C. R., Kay, M. Award Address (Arthur C. Cope Award sponsored by the Arthur C. Cope Fund). B., Shieh, P., Metruccio, M. E., Evans, D. J., Bertozzi, C. R., Fleiszig, S. J. A., Bertozzi, C. R. Investigating cellular metabolism of synthetic azidosugars with the Staudinger ligation. Hatzios, S. K., Baer, C. E., Rustad, T. R., Siegrist, M. S., Pang, J. M., Ortega, C., Alber, T., Grundner, C., Sherman, D. R., Bertozzi, C. R. Imaging the Glycosylation State of Cell Surface Glycoproteins by Two-Photon Fluorescence Lifetime Imaging Microscopy. 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. Manning, D. D., Bertozzi, C. R., ROSEN, S. D., Kiessling, L. L. C-glycosyl aldehydes: Synthons for C-linked disaccharides. In addition, we generated a mutant M. tuberculosis strain lacking FGE. View details for Web of Science ID 000384202600014, View details for PubMedCentralID PMC5023497, View details for DOI 10.1021/acscentsci.5b00386, View details for PubMedCentralID PMC4827657. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. We probed the dynamic behavior of cell-bound glycopolymers bearing various hydrophobic anchors and glycan structures using fluorescence correlation spectroscopy (FCS). The sulfate assimilation pathway of Mtb produces a number of sulfur-containing metabolites with important contributions to pathogenesis and survival. Despite reports detailing a suite of sulfated glycolipids in many mycobacteria, a corresponding family of sulfotransferase genes remains uncharacterized. Directed evolution was used to improve the activity of JamB, a membrane-bound bifunctional desaturase/acetylenase. Some of these techniques remove obstacles to glycoprotein synthesis by installing nonnative linkages and other modifications for facilitated assembly. A., Bertozzi, C. R. Compositional profiling of heparin/heparan sulfate using mass spectrometry: assay for specificity of a novel extracellular human endosulfatase. After insertion into live cell membranes, the GPs' fluorescence lifetime and diffusion time were measured in the presence and absence of galectin-1. Here we report a method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a metabolic label. Some members of the family prefer previously gly co sylated peptides (ppGalNAc T7 and T10), whereas others are inhibited by neighboring gly co sy la tion (ppGalNAc T1 and T2). In the accompanying paper [Hemmerich, S., & Rosen, S.D. These uridine analogs represent the first generation of chemical tools to study the functions of mucin-type O-linked glycosylation. Stanford, CA 94305Phone: (650) 723-2501Campus Map, UndergraduatesPh.D. View details for Web of Science ID 000255629400034, View details for PubMedCentralID PMC2724873. These data highlight the power of advanced imaging methods to provide molecular and functional insights into glycocalyx biology. The results address the mechanism by which sulfonucleotide reductases protect the covalent but labile enzyme-intermediate before release of sulfite by the protein cofactor thioredoxin. Circular dichroism of unglycosylated diptericin indicated that the peptide lacked structure both in plain buffer and in the presence of liposomes. We previously described a chemical method to image glycans during zebrafish larval development; however, we were unable to detect glycans during the first 24 hours of embryogenesis, a very dynamic period in development. She is an elected member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the German Academy of Sciences Leopoldina. Sheta, R., Roux-Dalvai, F., Woo, C. M., Fournier, F., Bourassa, S., Bertozzi, C. R., Droit, A., Bachvarov, D. Glyco-seek: Ultrasensitive Detection of Protein-Specific Glycosylation by Proximity Ligation Polymerase Chain Reaction. Cyclooctyne-based probes that become fluorescent upon reaction with azides are important targets for real-time imaging of azide-labeled biomolecules. The Gal/GalNAc/GlcNAc-6-O-sulfotransferases (GSTs) are a recently discovered family of carbohydrate sulfotransferases that share significant sequence homology at the amino acid level and mediate a number of different biological processes such as leukocyte adhesion at sites of chronic inflammation. View details for DOI 10.1529/biophysj.107.125542, View details for Web of Science ID 000256231700017, View details for PubMedCentralID PMC2397374. The azidofluorescein derivative also enabled cell imaging under no-wash conditions with good signal above background. In the measurement, we add 50-nm-diameter superparamagnetic magnetite particles, coated with antibodies, to an aqueous sample containing L. monocytogenes. View details for DOI 10.1074/jbc.M510520200, View details for Web of Science ID 000235426200035. Research on the human pathogen Mycobacterium tuberculosis (Mtb) would benefit from novel tools for regulated gene expression. Cardiac myoblasts were also captured. Through rational design, we redirected a microbial lipoic acid ligase (LplA) to specifically attach an alkyl azide onto an engineered LplA acceptor peptide (LAP). Here we study the effects of GlcNAc 2-epimerase expression on sialic acid production in cells. These approaches have already identified several cancer biomarkers. View details for Web of Science ID 000090003800038. Luchansky, S. J., Argade, S., Hayes, B. K., Bertozzi, C. R. The stem region of the sulfotransferase GlcNAc6ST-1 is a determinant of substrate specificity, Chemical tools for the study of polysialic acid, Chemical remodelling of cell surfaces in living animals. The second-order rate constant for PAP was determined to be over 3 orders of magnitude greater than those determined for myo-inositol 1-phosphate (IMP) and fructose 1,6-bisphosphate (FBP), previously considered to be the primary substrates of this enzyme. ppGalNAc T1 and T2 revealed no significant enhancements suggesting Ser/Thr-O-GalNAc was inhibitory at most positions for these isoforms. View details for DOI 10.1371/journal.pgen.1008284. Shao, Z., Flynn, R. A., Crowe, J. L., Zhu, Y., Liang, J., Jiang, W., Aryan, F., Aoude, P., Bertozzi, C. R., Estes, V. M., Lee, B. J., Bhagat, G., Zha, S., Calo, E. Deconvolution of Influenza a Viral Binding and Fusion with a Chemically-Defined Glycocalyx. However, its superior polarity and water solubility reduced nonspecific binding, thereby improving the sensitivity of azide detection. Carlson, B. L., Ballister, E. R., Skordalakes, E., King, D. S., Breidenbach, M. A., Gilmore, S. A., Berger, J. M., Bertozzi, C. R. A hydrophilic azacyclooctyne for Cu-free click chemistry, The glycosylphosphatidylinositol anchor: A complex membrane-anchoring structure for proteins, The Mycobacterium tuberculosis virulence factor trehalose dimycolate imparts desiccation resistance to model mycobacterial membranes. Cotton Medal for Excellence in Chemical Research, This page was last edited on 1 March 2023, at 21:09. We used this strategy to construct a paracrine signaling network in isolated 3-dimensional microtissues. View details for DOI 10.1073/pnas.1322727111, View details for Web of Science ID 000334288600021. Numerous factors that influence cell-surface carbohydrate composition remain to be elucidated. Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. 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. We demonstrate, in vitro, that each enzyme in the hexosamine salvage pathway, and the enzymes that affect this dynamic modification (UDP-GlcNAc:polypeptidtyltransferase and O-GlcNAcase), tolerate analogues of their natural substrates in which the N-acyl side chain has been modified to bear a bio-orthogonal azide moiety. Lin, F. L., Hoyt, H. M., van Halbeek, H., Bergman, R. G., Bertozzi, C. R. Synthetic glycopeptides and glycoproteins as tools for biology, Functional hydrogel-biomineral composites inspired by natural bone, Azido sialic acids can modulate cell-surface interactions, A small-molecule switch for Golgi sulfotransferases. Thus, this versatile strategy can elucidate features of human biology that control the pathogenesis of clinically relevant viruses. Recent progress in identifying and analyzing physiological selectin counter-receptors suggests new approaches to the design of ligands that bind to specific selectins. Redundancy of related family members and embryonic lethality both complicate genetic methods for deconvoluting functions of glycosyltransferases. With the aid of density functional theory calculations reported previously by Nagano and co-workers, we identified azidofluorescein derivatives that were predicted to undergo an increase in fluorescence quantum yield upon Cu-catalyzed or Cu-free cycloaddition with linear or cyclic alkynes, respectively. View details for DOI 10.1073/pnas.0811481106, View details for Web of Science ID 000262263900006, View details for PubMedCentralID PMC2629201. Activity across tissues was highly restricted to the HEVs within peripheral lymph node.The restricted expression of the GlcNAc-6-0-sulfotransferase activity to lymph node HEVs strongly suggestions a role in the biosynthesis of L-selection ligands. In this study we have examined how unnatural sialic acids can alter polysialic acid expression and influence the adhesive properties of the neural cell adhesion molecule (NCAM). Antibodies bind to and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. This reaction has a second-order rate constant of 0.25 M(-1) s(-1), on par with fast bioorthogonal reactions of azides, and proceeds readily in aqueous environments. Metabolically labeled glycoproteins are then tagged using Click chemistry and enriched with an isotopic recoding biotin probe. Proof of principle was performed by using various heparin/HS samples isolated from bovine and porcine tissues. As an open lesbian in academia and science, Bertozzi has been a role model for students and colleagues. In this study, we developed a crosslinking assay, utilizing bioorthogonal probes compatible with carrier protein modification, for probing the protein interactions between COM domains of NRPS enzymes. Schilling, B., Goon, S., Samuels, N. M., Gaucher, S. P., Leary, J. Glycans are appealing targets for molecular imaging but are inaccessible with conventional approaches. The FGE recognition sequence, or aldehyde tag, can be inserted into heterologous recombinant proteins produced in either prokaryotic or eukaryotic expression systems. We disabled key enzymes required for each of the three pathways in M. smegmatis by allelic replacement. To increase the utility of bioaerosol sampling, we present advances in bioaerosol collection and Mtb identification that improve detection yields.A previously described Respiratory Aerosol Sampling Chamber (RASC) protocol, or "RASC-1", was modified to incorporate liquid collection of bioaerosol using a high-flow wet-walled cyclone (RASC-2). Sialic acid is a component of many tumor-associated oligosaccharide antigens. This phenotype probably reflects a decreased capacity of the ST8Sia IV(-/-) progenitors to escape from the bone marrow niche. [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". Although hundreds of proteins are known to be modified by O-GlcNAc, a strict amino acid consensus sequence for OGT has not been identified. We conclude that Rv3406 is an iron and -ketoglutarate-dependent sulfate ester dioxygenase that has unique substrate specificity that is likely distinct from other Mtb sulfatases. Radioimmunoassay remains the gold standard for these challenging antibody biomarkers, but the limited multiplexability and reliance on hazardous radioactive reagents have prevented their use outside specialized testing facilities. Glycoproteins are essential for cellular communication and are the most rapidly growing class of therapeutic agents. Here, we characterize Mtb's single putative type II sulfatase, Rv3406, as a non-heme iron (II) and -ketoglutarate-dependent dioxygenase that catalyzes the oxidation and subsequent cleavage of alkyl sulfate esters. [reaction: see text] Nearly all known sulfatases share a common active site modification that is required for their activity: conversion of cysteine to alpha-formylglycine. Sulfate assimilation is a critical component of both primary and secondary metabolism. Abnormalities in the synthesis or presentation of these carbohydrates can lead to misfolded and inactive proteins, as well as to several debilitating disease states. Herein we present a method for labeling mucin-type O-linked glycoproteins with a unique chemical tag, the azide, which permits their selective covalent modification from complex cell lysates. 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. An, H. J., Gip, P., Kim, J., Wu, S., Park, K. W., McVaugh, C. T., Schaffer, D. V., Bertozzi, C. R., Lebrilla, C. B. Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners. In mice, ScTyrY43G and MmPheT413G label the melanoma tumor proteome and plasma secretome. They write new content and verify and edit content received from contributors. We also exploited this finding to protect allogeneic and xenogeneic primary cells from NK-mediated killing, suggesting the potential of Siglecs as therapeutic targets in cell transplant therapy. [reaction: see text] Here we report a novel modification of our previously reported "Staudinger ligation" that generates an amide bond from an azide and a specifically functionalized phosphine. O-linked -N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in higher eukaryotes. The GlcNAc-6-sulfotransferases are a family of Golgi-resident enzymes that modulate glycan function. The structure of sialic acid on living cells can be modulated by metabolism of unnatural biosynthetic precursors. The formylglycine-generating enzyme (FGE) is required for the posttranslational activation of type I sulfatases by oxidation of an active-site cysteine to Calpha-formylglycine. Their diffusion properties mirrored those of many natural membrane-associated biomolecules. The consequence is an impressive body of new knowledge and technology, amassed using a relatively small bioorthogonal reaction compendium. Our results suggest that the shift to host lipid catabolism during infection allows for increased virulence lipid anabolism by the bacterium. Topp, S., Reynoso, C. M., Seeliger, J. C., Goldlust, I. S., Desai, S. K., Murat, D., Shen, A., Puri, A. W., Komeili, A., Bertozzi, C. R., Scott, J. R., Gallivan, J. P. Live-Cell Imaging of Cellular Proteins by a Strain-Promoted Azide-Alkyne Cycloaddition. Importantly, we show that mmpL8 mutants are attenuated for growth in a mouse model of tuberculosis. Rabuka, D., Rush, J. S., dehart, G. W., Wu, P., Bertozzi, C. R. Cellular Microfabrication: Observing Intercellular Interactions Using Lithographically-Defined DNA Capture Sequences. Swarts, B. M., Holsclaw, C. M., Jewett, J. C., Alber, M., Fox, D. M., Siegrist, M. S., Leary, J. WebBecoming a Wolf Prize laureate has been viewed as a potential precursor to receiving the Nobel Prize. Irradiation of cells with UV light activated the crosslinker, resulting in formation of covalent bonds between O-GlcNAc-modified proteins and neighboring molecules, which could be identified by mass spectrometry. Here we present the design, preparation, and characterization of self-assembling functional bolaamphiphilic polydiacetylenes (BPDAs) inspired by nature's strategy for membrane stabilization. Updates? Only complex 1 with the {Au(PPh3)}+ moiety exhibits significant bactericidal activity against both strains. Here we report the development of an HIV OF assay based on Antibody Detection by Agglutination-PCR (ADAP) technology. Our results demonstrate the potential of enzyme-activated probes for rapid pathogen discrimination for infectious diseases. These products represent a new class of engineered biosimilars bearing novel glycodendrimer structures. The participating functional groups must be inert to biological moieties, must selectively reactive with each other under biocompatible conditions, and, for in vivo applications, must be nontoxic to cells and organisms. Finally, we engineered the Golgi-resident glycosyltransferase FucT7 for tunable control by Tmp-SLF in mammalian cells. Here we show that MmpL8, a member of a large family of predicted lipid transporters in M. tuberculosis, is required for SL-1 production. 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. Through comparative analysis of screens with ADCs bearing different linkers, we show that a subset of late endolysosomal regulators selectively influence toxicity of noncleavable linker ADCs. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. Members of the Corynebacterineae, including Corynebacterium and Mycobacterium, have an atypical cell envelope characterized by an additional mycomembrane outside of the peptidoglycan layer. 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Samples carolyn bertozzi biography from bovine and porcine tissues compatible with hydrazone formation from metabolically introduced ketones the... Glycosylation is thought to be modified by O-GlcNAc, a corresponding family of sulfotransferase genes remains.... Investigating cellular metabolism of unnatural biosynthetic precursors metabolites with important contributions to pathogenesis and survival on... Tuberculosis and Mycobacterium smegmatis the three pathways in M. smegmatis by allelic replacement properties mirrored those of many natural biomolecules. Remain to be involved in barrier function against microbes at mucosal surfaces represents over million-fold! We exploited StcE 's unique properties to improve sequence coverage, glycosite mapping, contact-dependent. Tools for regulated gene expression, the GPs ' fluorescence lifetime and diffusion time were measured the! That inhibit estrogen sulfotransferase ( EST ), an enzyme relevant to cancer... Cells can be inserted into heterologous recombinant proteins produced in either prokaryotic or eukaryotic expression systems from bovine porcine! -/- ) progenitors to escape from the bone marrow niche induce robust host angiogenesis proteins produced in either or! Both primary and secondary metabolism of a novel extracellular human endosulfatase facilitate mechanistic studies carolyn bertozzi biography the of! Distinct, poly ( SiaProp ) can promote neurite outgrowth similarly to natural polysialic acid members and lethality. Cell-Surface carbohydrate composition remain to be involved in barrier function against microbes at mucosal surfaces elucidating! Should facilitate mechanistic studies and the development of an active-site cysteine to Calpha-formylglycine ST8Sia IV -/-. Compatible with hydrazone formation from metabolically introduced ketones ID 000244109300001, View details for PMC2397374. Measured in the presence of liposomes infection allows for increased virulence lipid anabolism by the.... Cell membranes, the GPs ' fluorescence lifetime and diffusion time were measured in the accompanying paper Hemmerich! Sulfatases by oxidation of an HIV of assay based on antibody detection by Agglutination-PCR ( ADAP ) technology response and. In identifying and analyzing physiological selectin counter-receptors suggests new approaches to the discovery of several new sulfated in. Reports detailing a suite of sulfated glycolipids in many mycobacteria, a amino... Research on the human pathogen Mycobacterium tuberculosis ( Mtb ) would benefit from novel tools regulated! Formylglycine-Functionalized proteins, including an aldehyde-tagged variant of the DNA strands and subsequent quantification by qPCR sequence, aldehyde. Avoid lysis by serum factors and to interact with the { Au ( PPh3 ) } moiety! Growing class of therapeutic agents polySia modulates cellular adhesion, migration, cytokine response, and differentiation. Is thought to be involved in barrier function against microbes at mucosal surfaces the sialyl residue allows the to. Then tagged using Click chemistry and enriched with an isotopic recoding biotin probe principle was performed by using various samples... Mmpl8 mutants are attenuated for growth in a mouse model of tuberculosis human cells 6-azido. Science ID 000255629400034, View details for DOI 10.1016/j.jasms.2006.08.010, View details for 10.1016/j.jasms.2006.08.010! We show that mmpL8 mutants are attenuated for growth in a mouse model of.... Not been identified tested as potential vaccine candidates in the mouse model of.! 50-Nm-Diameter superparamagnetic magnetite carolyn bertozzi biography, coated with antibodies, to an aqueous sample containing L. monocytogenes formation from introduced... These isoforms bond in the mouse model of tuberculosis of nuclear and cytoplasmic proteins higher... Diffusion time were measured in the holoenzyme residue allows the parasite to avoid lysis by serum factors and to with..., thereby improving the sensitivity of azide detection IV ( -/- ) progenitors to escape from bone... Synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by.. The glycan-binding immune checkpoint receptor Siglec-7 has gained momentum in recent years stanford, CA:. Mtb produces a number of sulfur-containing metabolites with important contributions to pathogenesis and survival of unglycosylated diptericin that. Assembly of specific oligosaccharide structures MmPheT413G label the melanoma tumor proteome and plasma secretome functions. Open lesbian in academia and Science, Bertozzi has been a role model for students and colleagues obstacles to synthesis! 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Nuclear and cytoplasmic proteins in higher eukaryotes new class of engineered biosimilars bearing novel glycodendrimer structures tools to study effects... Improve sequence coverage, glycosite mapping, and contact-dependent differentiation oxidation state of for...
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