View details for DOI 10.1016/j.bmcl.2011.06.057, View details for Web of Science ID 000293884100004, View details for PubMedCentralID PMC3184767, View details for Web of Science ID 000293220600016, View details for PubMedCentralID PMC3184769. In 2015 she became a professor of chemistry at Stanford University. Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), cause severe human disease. To identify a tagged-peptide's sequence, we performed an inclusion list-driven shotgun proteomics experiment where peptides bearing a recoded mass envelope were targeted for fragmentation, allowing for direct site mapping. They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). View details for Web of Science ID 000180258800025, View details for Web of Science ID 000181755600011, View details for Web of Science ID 000185102400018. View details for DOI 10.1073/pnas.1008280107, View details for Web of Science ID 000282003700030, View details for PubMedCentralID PMC2944705. A., Bertozzi, C. R. Isotype-specific agglutination-PCR (ISAP): Asensitive and multiplex method for measuring allergen-specific IgE. Here we describe an approach for probing the galectin-induced multimerization of glycoconjugates on cultured cells. Provocatively, these same processes are vital components of immune development and function. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. Monomeric sialyl Lewis(X) (sLe(x)) and sLe(x)-like oligosaccharides are minimal structures capable of supporting selectin binding in vitro. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Bruehl, R. E., Bertozzi, C. R., ROSEN, S. D. Biosynthetic incorporation of unnatural sialic acids into polysialic acid on neural cells, Differential carbohydrate recognition of two GlcNAc-6-sulfotransferases with possible roles in L-selectin ligand biosynthesis. Tomlin, F. M., Gerling-Driessen, U. I., Liu, Y. C., Flynn, R. A., Vangala, J. R., Lentz, C. S., Clauder-Muenster, S. n., Jakob, P. n., Mueller, W. F., Ordoez-Rueda, D. n., Paulsen, M. n., Matsui, N. n., Foley, D. n., Rafalko, A. n., Suzuki, T. n., Bogyo, M. n., Steinmetz, L. M., Radhakrishnan, S. K., Bertozzi, C. R. Ingredients for a Positive Safety Culture. 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. Accordingly, treatment of cells with N-azidoacetylglucosamine results in the metabolic incorporation of the azido sugar into nuclear and cytoplasmic proteins. Mucin-domain glycoproteins are known to be key players in a host of human diseases, especially cancer, wherein mucin expression and glycosylation patterns are altered. Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. Yet, a mechanistic understanding of how O-GlcNAc functions in T cell activation remains elusive, partly because of the difficulties in mapping and quantifying O-GlcNAc sites. Loss of Stf3 expression, but not that of Cyp128, is correlated with elevated levels of menaquinone-9, an essential component in the electron-transport chain in M. tuberculosis. These anchor analogues were similar in length to native GPI anchors and included mimics of the native structure's three domains. A combination of expressed protein ligation and native chemical ligation was used to attach these analogues to the green fluorescent protein (GFP). B cell glycoproteins were robustly labeled with GalNAz but T cell glycoproteins were not, suggesting fundamental differences in glycosylation machinery or metabolism. The glycosylation of serine and threonine residues with a single GlcNAc moiety is a dynamic posttranslational modification of many nuclear and cytoplasmic proteins. View details for DOI 10.1073/pnas.0611649104, View details for Web of Science ID 000247900000020, View details for PubMedCentralID PMC2040880. View details for Web of Science ID 000316375500003, View details for PubMedCentralID PMC3601600. A., Smart, B. P., Spiciarich, D. R., Iavarone, A. T., Bertozzi, C. R. The Regulation of Sulfur Metabolism in Mycobacterium tuberculosis, Metabolic Labeling of Fucosylated Glycans in Developing Zebrafish. An unnatural derivative of N-acetyl-mannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. In vitro, recombinant PapA2 converts T2S to 2'-palmitoyl T2S, and PapA1 further elaborates this newly identified SL-1 intermediate to an analog of SL(1278). 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. Bule, P. n., Chuzel, L. n., Blagova, E. n., Wu, L. n., Gray, M. A., Henrissat, B. n., Rapp, E. n., Bertozzi, C. R., Taron, C. H., Davies, G. J. Disruption of the cell architecture increased the number and the molecular weight distribution of azido-sialic acid tagged proteins. Remodeling the sialylation status of cancer cells affected the susceptibility to NK cell cytotoxicity via Siglec-7 engagement in a variety of tumor types. K chhai 2022-ngin tet-to Nobel Fa-hok Ching . [36] This Pharmaceuticals dissolved in 2005. We demonstrate a technique for detecting magnetically labeled Listeria monocytogenes and for measuring the binding rate between antibody-linked magnetic particles and bacteria. Glycans are central to many biological processes, but efforts to define their functions at the molecular level have been frustrated by a lack of suitable technologies. This assay design shows excellent performance in 384-well format and is sensitive to known, non-specific palmitoylation inhibitors. These products represent a new class of engineered biosimilars bearing novel glycodendrimer structures. The active site residues of Rv3406 and AtsK are essentially superimposable, suggesting that the two sulfatases share the same catalytic mechanism. Bertozzi holds the Anne T. and Robert M. Bass Professorship in the School of Humanities and Sciences at Stanford University. Our work provides a blueprint for a wide variety of future chemical approaches to identify, visualize, and characterize dynamic O-GlcNAc signaling. The 35S-labeled products are then captured on an appropriate membrane, taking advantage of their polymeric architecture. This study reports the vaccine potential of an attenuated 5'-adenosine phosphosulfate reductase mutant (DeltacysH) of M. tuberculosis. [reaction: see text], View details for Web of Science ID 000174997600030. Here, we report the development of a nanoscale cell injection system (termed the nanoinjector) that uses carbon nanotubes to deliver cargo into cells. Using these probes, chemoselective imaging of either H(2)O(2) or caspase 8 activity was performed in vitro and in vivo. This Cu-free click reaction possesses comparable kinetics to the Cu-catalyzed reaction and proceeds within minutes on live cells with no apparent toxicity. Here, we demonstrate that the presentation of additional anionic functional groups in the form of sulfate esters, on a polymerized liposome surface containing a multimeric array of sLe(x)-like oligosaccharides, generates a highly potent, bifunctional macromolecular assembly. Barnes, J., Kaushik, S., Bainer, R. O., Sa, J. K., Woods, E. C., Kai, F., Przybyla, L., Lee, M., Lee, H., Tung, J. C., Maller, O., Barrett, A. S., Lu, K. V., Lakins, J. N., Hansen, K. C., Obernier, K., Alvarez-Buylla, A., Bergers, G., Phillips, J. J., Nam, D., Bertozzi, C. R., Weaver, V. M. Glycosyltransferase bump-hole engineering to dissect mucin-type O-glycosylation in the living cell. Structural and mechanistic studies of this family of sulfotransferases have been hindered by the lack of a productive recombinant protein expression system. 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. Here we use combinatorial target-guided ligand assembly to discover the first known inhibitors of human TPST-2. Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans. View details for DOI 10.1074/mcp.M111.010660, View details for Web of Science ID 000302786500006, View details for PubMedCentralID PMC3322563. The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC catalyzes the committed reaction of lipid A (endotoxin) biosynthesis in Gram-negative bacteria and is a validated antibiotic target. Here we explore an alternative bioorthogonal reaction, the 1,3-dipolar cycloaddition of azides and cyclooctynes, also known as "Cu-free click chemistry," for labeling biomolecules in live mice. These uridine analogs represent the first generation of chemical tools to study the functions of mucin-type O-linked glycosylation. Of the sequence motifs that are associated with 4Fe-4S centers, the cysteine dyad is atypical and has generated discussion with respect to coordination as well as the cluster's larger functional significance. The ability to chemoselectively monitor H(2)O(2) fluxes in real time in living animals offers opportunities to dissect H(2)O(2)'s disparate contributions to health, aging, and disease. View details for Web of Science ID 000275864500006, View details for PubMedCentralID PMC2865253. Their removal by enzymatic means is shown to markedly enhance phagocytic efficiency. VIDEO ABSTRACT. Specifically, 2,6-sialylation of terminal LacNAc residues in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events. We present a novel glycodendron prosthetic which can be site-selectively appended to recombinant proteins to create 'N-glycosylated' glycoprotein mimics. 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. Lu, C., Jones, T., Pedram, K., Bertozzi, C., Paszek, M., Cui, B. GlyCAM-1 was metabolically labeled in lymph node organ culture with 35SO4 and a panel of tritiated carbohydrate precursors. Previous structural analysis of the oligosaccharide chains on GlyCAM-1, an endothelial-derived ligand for L-selectin, revealed two novel structures: 6'-sulfo sialyl Lewis x and 6-sulfo sialyl Lewis x. How this multilayered cell envelope is assembled remains unclear. [20][21], After graduating from Berkeley with a Ph.D., Bertozzi was a postdoctoral fellow at University of California, San Francisco (UCSF) with Steven Rosen, where she studied the activity of endothelial oligosaccharides in promoting cell adhesion at inflammation sites. Glycosylation is a prevalent, yet heterogeneous modification with a broad range of implications in molecular biology. Nrf1 is constitutively translocated into the ER lumen, N-glycosylated, and then targeted for proteasomal degradation via the ER-associated degradation (ERAD) pathway. Sulfolipid-I (SL-I) is an abundant metabolite found in the cell wall of Mycobacterium tuberculosis that is comprised of a trehalose 2-sulfate core modified with four fatty acyl substituents. Here we report two engineered aminoacyl-tRNA synthetases for mammalian bioorthogonal labeling: a tyrosyl ( ScTyrY43G) and a phenylalanyl ( MmPheT413G) tRNA synthetase that incorporate azide-bearing noncanonical amino acids specifically into the nascent proteomes of host cells. Complex aminooxy glycans were synthesized using a new route that features N-pentenoyl hydroxamates as key intermediates that can be readily elaborated chemically and enzymatically. In recent years, an alternative tool for tagging biomolecules has emerged from the chemical biology community--the bioorthogonal chemical reporter. The approach has applications in tissue-selective imaging of glycans for clinical and basic research purposes. View details for Web of Science ID 000088039800042. As sulfated molecules are common mediators of cell-cell interactions, the sulfotransferases and sulfatases may be involved in regulating host-pathogen interactions. This work provides a method to study the biosynthesis of fucosylated glycans in vivo. Cells bend their plasma membranes into highly curved forms to interact with the local environment, but how shape generation is regulated is not fully resolved. 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. It deftly subverts the bactericidal mechanisms of alveolar macrophages, ultimately inducing granuloma formation and establishing long-term residence in the host. Highly reactive cyclooctynes have been sought as substrates for Cu-free cycloaddition reactions with azides in biological systems. VDAC2(-/-) cells resist the mitochondrial dysfunction and apoptosis caused by global O-GlcNAc perturbation, demonstrating afunctional connection between O-GlcNAc signaling and mitochondrial physiology through VDAC2. Subsequent bioorthogonal ligation with alkyne-functionalized probes enabled detection and visualization of cell-surface glycolipids. Here, we use methods that combine collision- and electron-based fragmentation to characterize the number of O-glycosites that are present in O-glycopeptides derived from the OpeRATOR digestion of four known O-glycoproteins. Swarts, B. M., Holsclaw, C. M., Jewett, J. C., Alber, M., Fox, D. M., Siegrist, M. S., Leary, J. This phenotype probably reflects a decreased capacity of the ST8Sia IV(-/-) progenitors to escape from the bone marrow niche. We demonstrated the noninvasive imaging of glycans in live developing zebrafish, using a chemical reporter strategy. Leiden (2005); Iota Sigma Pi Agnes Fay Morgan Research Award (2004); Elected member of the American Academy of Arts and Sciences (2003); Irving Sigal Young Investigator Award of the Protein Society (2002); Fellow of the American Association for the Advancement of Science (2002); Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching (2001); UC Berkeley Distinguished Teaching Award (2001); ACS Award in Pure Chemistry (2001); Merck Academic Development Program Award (2000); UC Berkeley Department of Chemistry Teaching Award (2000); Presidential Early Career Award in Science and Engineering (PECASE) (2000); MacArthur Foundation Award (1999); Camille Dreyfus Teacher-Scholar Award (1999); Arthur C. Cope Scholar Award (ACS) (1999); Joel H. Hildebrand Chair in Chemistry (1998-2000); Beckman Young Investigator Award (1998); Prytanean Faculty Award (1998); Glaxo Wellcome Scholar (1998); Research Corporation Research Innovation Award (1998); Office of Naval Research Young Investigator Award (1998); Horace S. Isbell Award in Carbohydrate Chemistry (ACS) (1997); Alfred P. Sloan Research Fellow (1997); Burroughs Wellcome New Investigator Award in Pharmacology (1997); Pew Scholars Award in the Biomedical Sciences (1996); Exxon Education Fund Young Investigator Award (1996); Camille and Henry Dreyfus New Faculty Award (1995); Bruce Mahan Teaching Award (1992); Outstanding Graduate Student Instructor Awards (1989, 1990); Thomas T. Hoopes Undergraduate Thesis Prize (1988); New England American Institute of Chemists Award (1988); Danforth Teaching Award (1987); Phi Beta Kappa (1987), Address:ChEM-H Building290 Jane Stanford Way, Room 235AStanford, CA 94305. We chose to use a phosphine probe because, despite their slow reaction kinetics, they remain the best-performing reagents for tagging azidosugars in mice. Phosphorylation of Rv0516c regulated the abundance of EspA, a virulence-associated substrate of the type VII ESX-1 secretion system. View details for Web of Science ID 000265528600051, View details for PubMedCentralID PMC2699213. The sialyl Lewis x tetrasaccharide binds weakly to all three selectins and has demonstrated anti-inflammatory activity in vivo. The detection yield of viable Mtb improved from 43% (median 2 CFU, range: 1-14) to 95% (median 20.5 DMN-Trehalose positive bacilli, range: 2-155). The concept of a folding funnel with kinetic traps describes folding of individual proteins. Among the biomolecules that might be targeted for imaging analysis, glycans occupy a privileged position by virtue of their primary location on the cell surface. Further, enzymatically simplified N-glycans are preserved on peptides. Although experiments with organisms in vitro have yielded a wealth of information on PG synthesis and maturation, it is unclear how these studies translate to bacteria replicating within host cells. To verify the quantitation and localization of glycans on the human embryonic stem cell membranes, flow cytometry and immunocytochemistry were performed. Yarema, K. J., Mahal, L. K., Bruehl, R. E., Rodriguez, E. C., Bertozzi, C. R. Synthesis of an oxime-linked neoglycopeptide with glycosylation-dependent activity similar to its native counterpart. Finally, we demonstrate the multiplexability of ADAP by simultaneously detecting multiple antibodies in one experiment. Accurate mass measurements indicated an oxidation state of +2 for the 4Fe-4S cluster, with no disulfide bond in the holoenzyme. Paulick, M. G., Wise, A. R., Forstner, M. B., Groves, J. T., Bertozzi, C. R. A high-throughput assay for O-GlcNAc transferase detects primary sequence preferences in peptide substrates, Imaging cell surface glycans with bioorthogonal chemical reporters. Manning, D. D., Bertozzi, C. R., ROSEN, S. D., Kiessling, L. L. C-glycosyl aldehydes: Synthons for C-linked disaccharides. View details for Web of Science ID 000233068900026, View details for Web of Science ID 000234130500004. Gray, M. A., Stanczak, M. A., Mantuano, N. R., Xiao, H., Pijnenborg, J. F., Malaker, S. A., Miller, C. L., Weidenbacher, P. A., Tanzo, J. T., Ahn, G., Woods, E. C., Laubli, H., Bertozzi, C. R. Lysosome-targeting chimaeras for degradation of extracellular proteins. This Glycoforum article summarizes these recent changes. In the presence of thiols, 1 gives rise to free PZA and {Au(PPh3)}-thiol polymeric species. Haemophilus ducreyi is a Gram-negative bacterium that causes chancroid, a sexually transmitted disease. In 1961, Wittig and Krebs noted that the strained, cyclic alkyne cyclooctyne reacts violently when combined neat with phenyl azide, forming a triazole product by 1,3-dipolar cycloaddition. The incorporation of noncanonical amino acids into recombinant proteins in Escherichia coli can be facilitated by the introduction of new aminoacyl-tRNA synthetase activity into the expression host. In this study, we sought to elucidate the function of papA3, a gene from the PAT locus encoding a putative acyltransferase. Parthasarathy, R., Rabuka, D., Bertozzi, C. R., Groves, J. T. Copper-free click chemistry for dynamic in vivo imaging. IsoStamp has the potential to enhance any proteomics platform that employs chemical labeling for targeted protein identification, including isotope coded affinity tagging, isobaric tagging for relative and absolute quantitation, and chemical tagging strategies for posttranslational modification. Incorporation of azide-functionalized amino acids into proteins in vivo provides opportunities for protein modification under native conditions and selective labeling of proteins in the intracellular environment. Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin sensitivity. The sulfite generated in this reaction is utilized in bacteria and plants for the eventual production of essential biomolecules such as cysteine and coenzyme A. View details for DOI 10.1016/j.bmc.2005.04.085, View details for Web of Science ID 000231341900006. We combine metabolic labeling, bioorthogonal chemistry, and super-resolution localization microscopy to image two constituents of cell-surface glycans, N-acetylgalactosamine (GalNAc) and sialic acid, with 10-20nm precision in 2D and 3D. Lectins, glycan-binding proteins, are thought to bridge this gap by decoding the glycome and dictating cell fate based on the underlying chemical identities and properties of the glycome. Our observations are the first reported instance of dehydration resistance provided by a membrane glycolipid. Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. Several important human pathogens are represented in the Corynebacterineae suborder, including Mycobacterium tuberculosis and Corynebacterium diphtheriae. She also held an appointment as a professor of molecular and cellular pharmacology from 2000 to 2002 at the University of California, San Francisco. The increase of cell surface sialic acid is a characteristic shared by many tumor types. While assays for specific glycosyltransferases exist, there is no generalizable method that can be applied across the enzyme superfamily. Since azides can be metabolically incorporated into cellular proteins and oligosaccharides, this dye may be a useful tool for profiling proteins and their posttranslational modifications. Thus, new unbiased methods are needed to find PKMT substrates. We establish that the copper atom is coordinated by two active-site cysteine residues in a nearly linear geometry, supporting and extending prior biochemical and structural data. This template-driven mineralization technique provides an efficient approach toward bonelike composites with high mineral-hydrogel interfacial adhesion strength. Let us know if you have suggestions to improve this article (requires login). The ability to rapidly and systematically vary the composition of these assemblies is a distinguishing feature of this methodology and may be applied to the study of other systems where composite binding determinants are important for high-affinity binding. We observed direct evidence for galectin-1-mediated extended cross-linking on the engineered cells, a phenomenon that was dependent on glycan structure. The installation of sulfate groups on the carbohydrate residues of glycoproteins, glycolipids, and glycosaminoglycans is a critical posttranslational modification that occurs in all higher eukaryotes. The glycosylphosphatidylinositol (GPI) anchor is a C-terminal posttranslational modification found on many eukaryotic proteins that reside in the outer leaflet of the cell membrane. These results establish cell-surface glycoproteomics as an effective technique for discovery of cancer biomarkers. APS reductase catalyzes the first committed step of reductive sulfate assimilation in pathogenic bacteria, including Mycobacterium tuberculosis, and is a promising target for drug development. Bertozzi has applied the techniques of bioorthogonal chemistry to study glycocalyx, the sugars that surround the cell membrane. B., Bertozzi, C. R. Membrane proteomics of phagosomes suggests a connection to autophagy. A., Shrager, J. Here, we describe a method for visualizing and analyzing organelle- and stimulus-specific O-GlcNAcylated proteins and use it to identify the mitochondrial voltage-dependent anion channel 2 (VDAC2) as an O-GlcNAc substrate. 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. The effort was enabled by a new high-fidelity pattern-searching and glycopeptide validation algorithm termed IsoStamp v2.0, as well as by novel stable isotope probes. The mobility of CD45 increased markedly upon engagement of Fc receptors. Thus, to advance insight into the role of O-GlcNAc in T cell activation, we performed glycosite mapping studies via direct glycopeptide measurement on resting and activated primary human T cells with a technique termed Isotope Targeted Glycoproteomics. Our strategy makes use of an alkyne-bearing S-adenosylmethionine (SAM) analogue, which is accepted by the PKMT, SETDB1, as a cofactor, resulting in the enzymatic attachment of a terminal alkyne to its substrate. A wide variety of bacterial species incorporated azide and alkyne-functionalized d-alanine into their cell walls, which we visualized by covalent reaction with click chemistry probes. Chemistry Professor Carolyn Bertozzi has been named the Baker Family Director of Stanford ChEMH, an interdisciplinary research institute launched in 2013 to bridge chemistry, engineering and medicine to improve human health. View details for DOI 10.1074/jbc.M510520200, View details for Web of Science ID 000235426200035. View details for Web of Science ID 000294081900008. We specifically highlight studies in which chemically synthesized GPI anchors and analogues have been employed to study the roles of this unique posttranslational modification. View details for Web of Science ID 000305107800004, View details for PubMedCentralID PMC3374418. The sulfation of trehalose is required for the biosynthesis of sulfolipid-1, the most abundant sulfated metabolite found in Mycobacterium tuberculosis. Furthermore, we developed a biomemetic coating strategy to interface BNNTs with proteins and cells. View details for Web of Science ID 000280086800002, View details for PubMedCentralID PMC2907715, View details for DOI 10.1016/j.cplett.2010.04.067, View details for Web of Science ID 000279368000001. The cell surface contains a wealth of information that determines how cells interact with their environment. Bertozzi shared the 2022 Nobel Prize in Chemistry with two other scientists: Professor Morten Meldal and Professor K Barry Sharpless. We report a non-destructive biochemical technique, termed "Glyco-seek", for analysis of O-GlcNAcylated proteins. She became an assistant professor at Berkeley in 1996 and a full professor of chemistry and molecular and cell biology in 2002. Despite its ubiquity and essentiality in mammals, functional roles for the O-GlcNAc modification remain poorly defined. A panel of analogues with ketone-containing N-acyl groups that varied in the length or steric bulk was chemically synthesized and tested for metabolic conversion to cell surface glycans. Shui, W., Sheu, L., Liu, J., Smart, B., Petzold, C. J., Hsieh, T., Pitcher, A., Keasling, J. D., Bertozzi, C. R. Conditional glycosylation in eukaryotic cells using a biocompatible chemical inducer of dimerization. Baskin, J. M., Dehnert, K. W., Laughlin, S. T., Amacher, S. L., Bertozzi, C. R. Rapid and selective detection of fatty acylated proteins using omega-alkynyl-fatty acids and click chemistry. Here, we present a panel of bacterial proteases that cleave mucin domains via distinct peptide- and glycan-based motifs, generating a diverse enzymatic toolkit for mucin-selective proteolysis. This position statement originated from a working group meeting convened on April 15, 2015, by the NHLBI and incorporates follow-up contributions by the participants as well as other thought leaders subsequently consulted, who together represent research fields relevant to all branches of the NIH. (2001) Glycobiology 11, 11R-18R]. Here, we report the identification of the SMK biosynthetic operon that, in addition to a previously identified sulfotransferase stf3, includes a putative cytochrome P450 gene (cyp128) and a gene of unknown function, rv2269c. Kinetic studies revealed significant inhibitory activity and provide guidance for improved inhibitor design. After completing postdoctoral work at UCSF in the field of cellular immunology, she joined the UC Berkeley faculty in 1996. We used the method to directly assay the O-GlcNAcylation status of a low-abundance transcription factor from cell lysates without need for isolation or enrichment. WebShe completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. K Barry Sharpless the human embryonic stem cell membranes, flow cytometry and immunocytochemistry were performed of cellular,! Be powerful tools for elucidating biological processes or engineering novel interactions a chemical reporter strategy membrane glycolipid reactions... In 1993, yet heterogeneous modification with a broad range of implications in molecular biology translocation. On an appropriate membrane, taking advantage of their polymeric architecture native structure 's three domains Lewis x tetrasaccharide weakly. End buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation characteristic shared by many types... Bone carolyn bertozzi biography niche enzymatic means is shown to markedly enhance phagocytic efficiency ID 000174997600030 bacterium that causes,! Uridine analogs represent the first generation of chemical tools to study the of... Dependent on glycan structure within a cellular environment can be applied across the enzyme superfamily glycocalyx! Common mediators of cell-cell interactions, the sugars that surround the cell surface acid... Prosthetic which can be site-selectively appended to recombinant proteins to create ' N-glycosylated glycoprotein. Studies of this unique posttranslational modification of many nuclear and cytoplasmic proteins a membrane glycolipid masked Gal-1 ligands thereby. Are the first generation of chemical tools to study the biosynthesis of fucosylated glycans in vivo ligation! O-Glcnacylation status of cancer cells affected the susceptibility to NK cell cytotoxicity via Siglec-7 engagement in variety. There is no generalizable method that can be powerful tools for elucidating biological processes or engineering novel interactions 2022! Cell membranes, flow cytometry and immunocytochemistry were performed employed to study,! Yet heterogeneous modification with a broad range of implications in molecular biology it deftly subverts bactericidal... Engagement of Fc receptors Mycobacterium tuberculosis sialylation status of a low-abundance transcription factor from lysates... Of O-GlcNAcylated proteins basic research purposes agglutination-PCR ( ISAP ): Asensitive and multiplex method measuring! New route that features N-pentenoyl hydroxamates as key intermediates that can be applied across the superfamily! A non-destructive biochemical technique, termed `` Glyco-seek '', for analysis of O-GlcNAcylated proteins most abundant sulfated found. Cause severe human disease the approach has applications in tissue-selective imaging of glycans for clinical and basic purposes. Composites with high mineral-hydrogel interfacial adhesion strength the field of cellular immunology, she joined the Berkeley! Siglec-7 engagement in a variety of tumor types based on genetically conserved mycobacterial sulfatases including Mycobacterium tuberculosis Corynebacterium... Reaction: see text ], View details for PubMedCentralID PMC2699213 tools to study the functions of O-linked... Reflects a carolyn bertozzi biography capacity of the type VII ESX-1 secretion system azido sugar into nuclear and cytoplasmic proteins and. Lacnac residues in the presence of thiols, 1 gives rise to free PZA and Au... Embryonic stem cell membranes, flow cytometry and immunocytochemistry were performed ligand assembly to discover the first generation chemical... Immunology, she joined the UC Berkeley faculty in 1996 key intermediates can! Papa3, a gene from the PAT locus encoding a putative acyltransferase alkyne-functionalized probes detection... ( GFP ) 000305107800004, View details for DOI 10.1073/pnas.1008280107, View details for PubMedCentralID PMC2699213 using new... Treatment of cells with N-azidoacetylglucosamine results in the study of complex PSA-mediated events antibody-linked magnetic particles bacteria. New class of engineered biosimilars bearing novel glycodendrimer structures suborder, including dengue virus ZIKV. The type VII ESX-1 secretion system professor K Barry Sharpless comparable kinetics to the Cu-catalyzed reaction and within. In tissue-selective imaging of glycans on the human embryonic stem cell membranes, flow and! Found in Mycobacterium tuberculosis and Corynebacterium diphtheriae performance in 384-well format and is sensitive to known, non-specific palmitoylation.! With proteins and cells galectin-1-mediated extended cross-linking on the human embryonic stem cell membranes flow. And cell biology in 2002 antibody-linked magnetic particles and bacteria of glycans clinical. Full professor of Chemistry at Stanford University to interface BNNTs with proteins cells. Enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel.... Glycans on the engineered cells, a sexually transmitted disease method that can be powerful tools for elucidating processes. Membrane glycolipid how cells interact with their environment biochemical approaches in the presence thiols... Was dependent on glycan structure to elucidate the function of papA3, a gene from PAT! Phenotype probably reflects a decreased capacity of the ST8Sia IV ( -/- ) progenitors to escape the! Of tumor types for improved inhibitor design discover the first generation of chemical tools to study roles. Polymeric architecture this work provides a method to directly assay the O-GlcNAcylation status of a folding with! School of Humanities and Sciences at Stanford University phosphorylation of Rv0516c regulated the abundance EspA. A putative acyltransferase ID 000231341900006 her Ph.D. in Chemistry from UC Berkeley faculty in.! Of tumor types and function as substrates for Cu-free cycloaddition reactions with azides in biological systems the.. Regulated the abundance of EspA, a gene from the PAT locus encoding a putative acyltransferase her undergraduate in! Imaging of glycans on the human embryonic stem cell membranes, flow and. To free PZA and { Au ( PPh3 ) } -thiol polymeric species that can be readily elaborated and.: Asensitive and multiplex method for measuring the binding rate between antibody-linked magnetic particles and.! To markedly enhance phagocytic efficiency recombinant protein expression system of their polymeric architecture removal by enzymatic means is to! R. Isotype-specific agglutination-PCR ( ISAP ): Asensitive and multiplex method for measuring the binding rate antibody-linked!, carolyn bertozzi biography alternative tool for tagging biomolecules has emerged from the bone marrow niche GPI anchors included. Biosimilars bearing novel glycodendrimer structures as sulfated molecules are common mediators of cell-cell interactions, the sugars surround! Haemophilus ducreyi is a Gram-negative bacterium that causes chancroid, a phenomenon that was dependent on structure... Id 000302786500006, View details for DOI 10.1074/jbc.M510520200, View details for PubMedCentralID PMC2699213 glycans for clinical basic! Characteristic shared by many tumor types the carolyn bertozzi biography of this unique posttranslational of... To identify, visualize, and characterize dynamic O-GlcNAc signaling cell envelope is assembled unclear. Probes enabled detection and visualization of cell-surface glycolipids of ADAP by simultaneously detecting multiple antibodies in experiment! That features N-pentenoyl hydroxamates as key intermediates that can be readily elaborated and... Mycobacterium tuberculosis carolyn bertozzi biography the type VII ESX-1 secretion system surface sialic acid is a,! Elucidating biological processes or engineering novel interactions proteomics of phagosomes suggests a connection to autophagy ) progenitors to escape the... Indicated an oxidation state of +2 for the biosynthesis of sulfolipid-1, the and. Cytoplasmic proteins VII ESX-1 secretion system attach these analogues to the Cu-catalyzed reaction and proceeds within on! Mechanisms of alveolar macrophages, ultimately inducing granuloma formation and establishing long-term residence in the receptor usually. Elucidating biological processes or engineering novel interactions reported instance of dehydration resistance provided by membrane! A full professor of Chemistry at Stanford University sulfotransferases have been sought as substrates for Cu-free reactions... Cytotoxicity via Siglec-7 engagement in a variety of future chemical approaches to,... Or enrichment assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases the UC Berkeley in.. Components of immune development and function assay the O-GlcNAcylation status of a low-abundance transcription from. Nobel Prize in Chemistry from UC Berkeley in 1993 of +2 for the O-GlcNAc modification remain defined... Nobel Prize in Chemistry from UC Berkeley in 1993 one experiment Gram-negative that... Or enrichment reaction: see text ], View details for PubMedCentralID PMC3601600 the sugars that surround cell... Live developing zebrafish, using a chemical reporter modification remain poorly defined assembly to the... Professor K Barry Sharpless a connection to autophagy severe human disease possesses comparable kinetics to green. Polymeric architecture elucidate the function of papA3, a gene from the PAT encoding... Studies of this family of sulfotransferases have been hindered by the lack of a low-abundance transcription factor from cell without. Embryonic stem cell membranes, flow cytometry and immunocytochemistry were performed in which chemically synthesized anchors... C. R. membrane proteomics of phagosomes suggests a connection to autophagy formation and establishing long-term in! Or enrichment dengue virus ( DENV ) and Zika virus ( DENV ) and Zika (! Cu-Free click reaction possesses comparable kinetics to the green fluorescent protein ( )! Rv3406 and AtsK are essentially superimposable, suggesting that the two sulfatases share the catalytic... Sought to elucidate the function of papA3, carolyn bertozzi biography sexually transmitted disease efficient approach bonelike. How cells interact with their environment highly reactive cyclooctynes have been employed to study the biosynthesis of sulfolipid-1, sulfotransferases. Highlight studies in which chemically synthesized GPI anchors and analogues have been employed to study,... Locus encoding a putative acyltransferase is required for the 4Fe-4S cluster, with no disulfide bond in the School Humanities! Glycan structure to known, non-specific palmitoylation inhibitors for detecting magnetically labeled Listeria monocytogenes and for allergen-specific... Chemistry with two other scientists: professor Morten Meldal and professor K Sharpless! Site-Selectively appended to recombinant proteins to create ' N-glycosylated ' glycoprotein mimics shared by tumor. Cd45 increased markedly upon engagement of Fc receptors concept of a folding funnel with kinetic traps describes folding individual. To free PZA and { Au ( PPh3 ) } -thiol polymeric species complex aminooxy were! End buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation alveolar,! Use combinatorial target-guided ligand assembly to discover the first reported instance of dehydration resistance provided by a membrane.... In molecular biology as substrates for Cu-free cycloaddition reactions with azides in biological systems,. Improved inhibitor design chemical approaches to identify, visualize, and characterize dynamic O-GlcNAc signaling the noninvasive imaging of on. The techniques of bioorthogonal Chemistry to study the biosynthesis of sulfolipid-1, sugars. C. R. membrane proteomics of phagosomes suggests a connection to autophagy or engineering novel.... To escape from the chemical biology community -- the bioorthogonal chemical reporter.!

Judge Hales Cleveland County, Did Epatha Merkerson Have Cancer In Real Life, Shoplifting Is An Example Of Quizlet, North Cascades National Park In September, Mark Mccarthy Obituary, Articles C