We found that extension of the N-acyl chain to six, seven, or eight carbon atoms dramatically reduced utilization by the biosynthetic machinery. Humans do not possess a homologous metabolic pathway, and thus, these enzymes represent attractive targets for therapeutic intervention. Prof. Bertozzi has been recognized with many honors and awards for both her research and teaching accomplishments. WebDr. Flynn, R. A., Belk, J. Unnatural sialic acids are generated by metabolic conversion of synthetic N-acyl mannosamines and are typically incorporated into cell-surface glycoconjugates. These two strategies provide a means to selectively modify cell-surface glycans with exogenous probes. Breidenbach, M. A., Gallagher, J. E., King, D. S., Smart, B. P., Wu, P., Bertozzi, C. R. Copper-free click chemistry in living animals. This platform offers a new approach to exploring the "galectin lattice" hypothesis and to defining galectin ligand specificity in a physiologically relevant context. In addition, GalNAz efficiently labeled mucin-type O-linked glycoproteins expressed at endogenous levels. Poor diagnostic tools to detect active disease plague TB control programs and affect patient care. The azide, being nonreactive within cells, was ideal for use in living systems. Here we present the first step toward bottom-up assembly of model cell surfaces-the synthesis of mucin mimetics and their incorporation into artificial membranes. 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 findings identify an osmosensory pathway orchestrated by PknD, Rv0516c, and SigF that enables adaptation to osmotic stress through cell wall remodeling and virulence factor production. 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. Dehnert, K. W., Beahm, B. J., Huynh, T. T., Baskin, J. M., Laughlin, S. T., Wang, W., Wu, P., Amacher, S. L., Bertozzi, C. R. Metabolic cross-talk allows labeling of O-linked beta-N-acetylglucosamine-modified proteins via the N-acetylgalactosamine salvage pathway. The compound potentiates the cytotoxicity of carfilzomib, a clinically used proteasome inhibitor, against MM and T cell-derived acute lymphoblastic leukemia (T-ALL) cell lines. Finally, we showed in a mouse model of infection that the loss of cyp128 exhibits a hypervirulent phenotype similar to that in previous studies of the stf3 mutant. In our approach, the glycosyltransferase is separated into two domains, one that determines localization and one responsible for catalysis. 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. To understand the adaptation of Mycobacterium tuberculosis to the intracellular environment, we used comprehensive metabolite profiling to identify the biochemical pathways utilized during growth on cholesterol, a critical carbon source during chronic infection. These results show that CysH is important for Mtb protection during the chronic infection phase, and that resistance to nitrosative and oxidative stress may be the mechanism of this protection. To verify the quantitation and localization of glycans on the human embryonic stem cell membranes, flow cytometry and immunocytochemistry were performed. This protocol outlines both the generation and the analysis of proteins aldehyde-tagged at their termini and the methods for chemical conjugation to the formylglycine. Riley, N. M., Bertozzi, C. R., Pitteri, S. J. This same structural diversity has imposed major challenges on the development of methods to study the intact glycoproteome. Lee, J. H., Baker, T. J., Mahal, L. K., Zabner, J., Bertozzi, C. R., WIEMER, D. F., Welsh, M. J. Exploiting differences in sialoside expression for selective targeting of MRI contrast reagents. She coined the term "bioorthogonal A total of 589 differentially expressed glycoproteins were identified upon GALNT3 KD. Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. [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. Bertozzi, C. R., Fukuda, S., ROSEN, S. D. CRACKING THE CARBOHYDRATE CODE FOR SELECTIN RECOGNITION, IDENTIFICATION OF THE SULFATED MONOSACCHARIDES OF GLYCAM-1, AN ENDOTHELIAL-DERIVED LIGAND FOR L-SELECTIN. Using this approach, femtomole quantities of several targeted peptides were identified in total mammalian cell lysate, while traditional data-dependent methods were unable to identify as many peptides. A mathematical model was developed and tested experimentally to evaluate the prospects of using cell surface ketones as targets for covalent small-molecule drug delivery. View details for Web of Science ID 000272845900011, View details for PubMedCentralID PMC2807738. Armstrong, J. I., Ge, X., Verdugo, D. E., Winans, K. A., Leary, J. Mycobacterial carbohydrate sulfotransferase Stf0 catalyzes the sulfuryl group transfer from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to trehalose. We developed a series of ligand-inducible riboswitches that control gene expression in diverse species of Gram-negative and Gram-positive bacteria, including human pathogens that have few or no previously reported inducible expression systems. Kiick, K. L., Saxon, E., Tirrell, D. A., Bertozzi, C. R. An inhibitor of the human UDP-GlcNAc 4-epimerase identified from a uridine-based library: A strategy to inhibit O-linked glycosylation, Homogeneous glycopeptides and glycoproteins for biological investigation. Cell surface trehalose mycolates are important modulators of mycobacterial pathogenesis and host immune response. View details for DOI 10.1002/cbic.200600224, View details for Web of Science ID 000241392400005. Sulfurcontaining molecules were initially identified by mass spectral analysis of cell extracts from bacteria labeled metabolically with a stable sulfur isotope (34SO 4 2-). Physiological blood-brain transport is impaired with age by a shift in transcytosis. These data provide strong evidence that Stf0 carries out the first committed step in the biosynthesis of SL-1 and establish a system for probing the role of SL-1 in M. tuberculosis infection. View details for DOI 10.1073/pnas.0809218105, View details for Web of Science ID 000260913800030, View details for PubMedCentralID PMC2579359. 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. It is hosted by the National Center for Biotechnology Information (NCBI) at the NCBI-Glycans Page (www.ncbi.nlm.nih.gov/glycans/snfg.html). Sanders, W. J., Katsumoto, T. R., Bertozzi, C. R., ROSEN, S. D., Kiessling, L. L. Synthesis of beta-C-glycosides of N-acetylglucosamine via Keck allylation directed by neighboring phthalimide groups. Spreading of a mycobacterial cell surface lipid into host epithelial membranes promotes infectivity. Higher order oligosaccharides were readily generated by alkylation of the corresponding 3-thioGalNAc with N-bromoacetamido sugars. The unnatural sialic acid analog, N-levulinoyl sialic acid (SiaLev), was incorporated into cell surface glycoconjugates including PSA by the incubation of cultured neurons with the metabolic precursor N-levulinoylmannosamine (ManLev). As most therapeutic glycoproteins are sialylated and require this saccharide for optimal pharmacokinetics, we targeted sialic acid as a host for azides using N-azidoacetylmannosamine (ManNAz) as a biosynthetic precursor. 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. Here we investigate the biosynthetic origin of H. ducreyi sialosides by metabolic incorporation studies using a panel of N-acylmannosamine and sialic acid analogues. The review discusses the significance of mucin-type O-linked glycosylation initiated by the polypeptide N-acetylgalactosaminyltransferases in biology and development of chemical tools to study these enzymes and their substrates. In this paper, an efficient enzyme kinetics assay for Stf0 using electrospray ionization (ESI) mass spectrometry is presented. "What the sugar coating on your cells is trying to tell you", "Carolyn R. Bertozzi Wins 2022 AAAS Lifetime Mentor Award", "Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality", Presidential Early Career Award for Scientists and Engineers, American Association for the Advancement of Science, National Organization of Gay and Lesbian Scientists and Technical Professionals, Dr H. P. Heineken Prize for Biochemistry and Biophysics, "Carolyn Bertozzi | Department of Chemistry", "Stanford chemist explains excitement of chemistry to students, the public", "Carolyn Bertozzi honored by GLBT organization", "Carolyn Bertozzi To Lead ACS Central Science | Chemical & Engineering News", "Alla lincea Carolyn Bertozzi uno dei Nobel per la Chimica 2022", "NOGLSTP to Honor Bertozzi, Gill, Mauzey, and Bannochie at 2007 Awards Ceremony in February", "Press release: The Nobel Prize in Chemistry 2022", "Carolyn Bertozzi' s Winding Road to an Extraordinary Career", "Carolyn Bertozzi | Lemelson-MIT Program", "Bednarski, pioneer of new cancer therapies, dies at 47", "Chemistry Nobelist Carolyn Bertozzi's years at UC Berkeley", "Former Berkeley Lab Scientist Carolyn Bertozzi Wins 2022 Nobel Prize in Chemistry", "NIHF Inductee Carolyn Bertozzi Invented Bioorthogonal Chemistry", "From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions", "Precision glycocalyx editing as a strategy for cancer immunotherapy", "Carolyn Bertozzi 2010 Lemelson-MIT Prize", "Rapid detection of Mycobacterium tuberculosis in sputum with a solvatochromic trehalose probe", "Thios Pharmaceuticals Targeting Sulfation Pathways", "Thios Pharmaceuticals | www.inknowvation.com", "Women in Biotechnology: Barred from the Boardroom", "InterVenn Biosciences | AI-Driven Mass Spectrometry", "Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis bioaerosols", "Lysosome Targeting Chimeras (LYTACs) for the Degradation of Secreted and Membrane Proteins", "Lilly Announces that Professor Carolyn Bertozzi has Resigned from its Board of Directors", "Harvard Phi Beta Kappa Inductees Announced | News | The Harvard Crimson", "Dr. Bertozzi to Speak at Drug Discovery Symposium", "Major Awards & Honors | College of Chemistry", "President Honors Outstanding Young Scientists", "AAAS Fellows Carolyn Bertozzi and K. Barry Sharpless Receive Nobel Prize in Chemistry | American Association for the Advancement of Science", "UC Berkeley chemist, biologist, entrepreneur awarded $500,000 LemelsonMIT Prize | Research UC Berkeley", "05.03.2005 Three UC Berkeley faculty named to National Academy of Sciences", "Ernst Schering Prize 2007 Schering Stiftung", "The Roy L. Whistler International Award in Carbohydrate Chemistry 2008", "Carolyn Bertozzi Wins Harrison Howe Award | February 23, 2009, Issue Vol. The preferred substrates and functions of the >20 isoforms in mammals are not well understood. A Bioorthogonal Reaction of N-Oxide and Boron Reagents. Applying IsoStamp, we were able to detect femtomole quantities of a single tagged protein from total mammalian cell lysates at signal-to-noise ratios as low as 2.5:1. Jolly, A. L., Agarwal, P., Metruccio, M. M., Spiciarich, D. R., Evans, D. J., Bertozzi, C. R., Fleiszig, S. M. Visualization of mycobacterial membrane dynamics in live cells. Our results suggest that 6-sulfo sLe(x) binds to L-selectin with higher affinity than does sLe(x) or 6'-sulfo sLe(x) and that sulfation of sLe(x) capping groups on GlyCAM-1 at the 6-position is important for L-selectin recognition. Accurate mass measurements indicated an oxidation state of +2 for the 4Fe-4S cluster, with no disulfide bond in the holoenzyme. Mockl, L., Pedram, K., Roy, A., Krishnan, V., Gustavsson, A., Dorigo, O., Bertozzi, C., Moerner, W. Enzyme toolkit for selective enrichment and analysis of mucin-domain glycoproteins. B., Bertozzi, C. R., Pitteri, S. J., Giaccia, A. J., Plevritis, S. K. Toward Point-of-Care Detection of Mycobacterium tuberculosis: A Brighter Solvatochromic Probe Detects Mycobacteria within Minutes. All three selectins recognize sulfated and sialylated derivatives of the Lewis x [Le(x):Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and Lewis a [Le(a): Gal beta 1-->3(Fuc alpha 1-->4)GlcNAc] trisaccharide cores with affinities in the millimolar range, and it is believed that variants of these structures are the carbohydrate determinants of selectin recognition. Robinson, P. V., Tsai, C., de Groot, A. E., McKechnie, J. L., Bertozzi, C. R. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis. The endoplasmic-reticulum-localized RNA-binding proteins vigilin and ribosome-binding protein 1 directly bound viral RNA and each acted at distinct stages in the life cycle of flaviviruses. New additions to the bioorthogonal chemistry compendium can advance biological research by enabling multiplexed analysis of biomolecules in complex systems. View details for Web of Science ID 000311072900014, View details for PubMedCentralID PMC3500440. WebThis years prize amount is 10 million Swedish kronor (about 920,000 U.S. dollars), to be shared equally between the three laureates. To verify incorporation of the nonnatural sugars at N-glycan core positions, endoglycosidase H (endoH)-digested peptides from a purified secretory glycoprotein, Ygp1, were analyzed by mass spectrometry. Our glycan-specific assay can be paired with traditional proximity ligation assays to simultaneously determine the change in total protein levels. She completed her undergraduate degree in Chemistry from Harvard University in 1988 and her Ph.D. in Chemistry from UC Berkeley in 1993. 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. These screens identified CD22, a canonical Bcell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. Chemistry Central Office Here, we show that Cu(I)-FGE is functional in O2 activation and reveal a high-resolution X-ray crystal structure of FGE in complex with its catalytic copper cofactor. These uridine analogs represent the first generation of chemical tools to study the functions of mucin-type O-linked glycosylation. A., Dube, D. H., Bertozzi, C. R. Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis. Kumar, P., Schelle, M. W., Jain, M., Lin, F. L., Petzold, C. J., Leavell, M. D., Leary, J. However, the specific glycoproteins that contribute to the cancer cell-surface sialylation are not well characterized, specifically in bona fide human disease tissue. 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. We synthesized a series of GPI-protein analogues bearing modified anchor structures that were designed to dissect the contribution of various glycan components to the GPI-protein's membrane behavior. However, little is known about how alterations in O-GlcNAc cycling affect human embryonic stem cell (hESC) neural differentiation. View details for Web of Science ID 000168383900005. Carolyn R. Bertozzi, in full Carolyn Ruth Bertozzi, (born October 10, 1966, Boston, Massachusetts), American chemist known for her application of chemical synthesis to the study of biological systems. She coined the term bioorthogonal chemistry to describe the use of click reactionsquick, simple chemical reactions to study living cells. Bhakta, S., Bartes, A., Bowman, K. G., Kao, W. M., Polsky, I., Lee, J. K., Cook, B. N., Bruehl, R. E., ROSEN, S. D., Bertozzi, C. R., Hemmerich, S. New directions in glycoprotein engineering, Minimal sulfated carbohydrates for recognition by L-selectin and the MECA-79 antibody. Because a sulfur auxotrophic strain is the only requirement of the approach, many microorganisms can be studied in this manner. A., Ge, Y. n., Gunawardena, J. n., Hendrickson, R. C., Hergenrother, P. J., Huber, C. G., Ivanov, A. R., Jensen, O. N., Jewett, M. C., Kelleher, N. L., Kiessling, L. L., Krogan, N. J., Larsen, M. R., Loo, J. Tuberculosis (TB) is the leading cause of death from an infectious bacterial disease. Collectively, these results indicate that the stem region of GlcNAc6ST-1 influences substrate specificity, independent of its role in dimerization or Golgi retention. The ESI-MS assay presented herein requires no chromophoric substrate or product, and the analysis time is very short. 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. In this Account, we focus on research in our laboratory that seeks to transform the study of glycan function from a challenge to routine practice. View details for Web of Science ID 000177962200018. Sulfite is then released in a thioredoxin-dependent manner. One reason for this lack of development is the dearth of assays to efficiently screen for small molecular inhibitors of palmitoylation. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a highly evolved human pathogen characterized by its formidable cell wall. The kinetic constants of Stf0 were measured, and the catalytic mechanism of the sulfuryl group transfer reaction was investigated in initial rate kinetics and product inhibition experiments. Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified proteins in the outer leaflet of the plasma membrane. We quantified the absolute number of ketone groups displayed on cell surfaces as a function of the concentration of ManLev in the medium. A chimeric enzyme comprising the stem region of GlcNAc6ST-1 inserted between the catalytic and transmembrane domains of GlcNAc6ST-2 had the same substrate preference as native GlcNAc6ST-1. In the 1990s, Dr. Bertozzi was studying glycans, carbohydrates that sit on the surfaces of proteins and cells, the functions of which were not wholly understood. We chemically fused a recombinant sialidase to the human epidermal growth factor receptor 2 (HER2)-specific antibody trastuzumab through a C-terminal aldehyde tag. Key advantages of DNA-directed cell binding include the ability to immobilize both adherent and non-adherent cells, to capture cells selectively from a mixed population, to tune the binding properties of the cells, and to reuse substrates prepared with widely available DNA printing technologies. View details for DOI 10.1073/pnas.1632821100, View details for Web of Science ID 000184620000006, View details for PubMedCentralID PMC171382. Recently, the ability to modify monosaccharide structures within cellular glycans through metabolic processes has offered a new avenue for biological studies. Current approaches offer a precision approaching that of genetic control. In particular, we show that the removal of mucins, which are overexpressed in cancer cells, facilitates their clearance. EM has long been the main technique for imaging cell structures with nanometer resolution but has lagged behind light microscopy in the crucial ability to make specific molecules stand out. The most potent examined, 1-68A, is a pH-dependent, two-step, covalent inhibitor of Escherichia coli LpxC that competes with UDP to bind the enzyme in the first step of inhibition. Here we study the effects of GlcNAc 2-epimerase expression on sialic acid production in cells. We combined CRISPR-Cas9 knockout screens with RNAsequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. Luchansky, S. J., Hang, H. C., Saxon, E., Grunwell, J. R., Danielle, C. Y., Dube, D. H., Bertozzi, C. R. Drug targeting Mycobacterium tuberculosis cell wall synthesis: Development of a microtiter plate-based screen for UDP-galactopyranose mutase and identification of an inhibitor from a uridine-based library. Liposomes displaying 3'-sulfo Lewis(X)-like oligosaccharides, on the other hand, show slight loss of binding with introduction of additional anionic functional groups for E- and P-selectin and negligible change for L-selectin. These results establish a platform for engineering S-layer assemblies with 3-D architecture. Thus, NGLY1 inhibition prevents Nrf1 activation and represents a new therapeutic approach for cancers that depend on proteasome homeostasis. By contrast, only GlcNAc-6-SO(4) appears to contribute to MECA-79 binding. This tutorial review will summarize the history of this emerging field, as well as recent progress in the development and application of bioorthogonal copper-free click cycloaddition reactions. Here we report an approach toward generating homogeneously glycosylated proteins that involves chemical attachment of aminooxy glycans to recombinantly produced proteins via oxime linkages. Bertozzi is the only female scientist to have been awarded a science Nobel prize this year, after an all-male line-up in 2021. Despite this wealth of disease-relevant targets, there are currently few effective pharmacological tools to interfere with protein palmitoylation. The expression of recombinant M. tuberculosis APS kinase provides a means for the discovery of inhibitors of this enzyme and thus of the biosynthesis of SL-1. We developed a new fluorophore-trehalose conjugate to visualize trehalose monomycolates of the mycomembrane using super-resolution microscopy. These findings suggest that high mannose glycans are the major component of cell surface glycosylation with even terminal glucoses. [35], In 2001, Bertozzi and Steve Rosen co-founded Thios Pharmaceuticals in Emeryville, California, the first company to target sulfation pathways. View details for Web of Science ID 000180258800025, View details for Web of Science ID 000181755600011, View details for Web of Science ID 000185102400018. Jacobs, C. L., Goon, S., Yarema, K. J., Hinderlich, S., Hang, H. C., Chai, D. H., Bertozzi, C. R. Biosynthesis of sialylated lipooligosaccharides in Haemophilis ducreyi is dependent on exogenous sialic acid and not mannosamine. Once introduced into target biomolecules, either metabolically or through chemical modification, the azide can be tagged with probes using one of three highly selective reactions: the Staudinger ligation, the Cu(I)-catalyzed azide-alkyne cycloaddition, or the strain-promoted [3 + 2] cycloaddition. 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. a nanoscience research center at Lawrence Berkeley National Laboratory. Carolyn earned Viral RNA-RNA and RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection. Chang, P. V., Dube, D. H., Sletten, E. M., Bertozzi, C. R. Progress and challenges for the bottom-up synthesis of carbon nanotubes with discrete chirality, Identification of glycoproteins targeted by Trypanosoma cruzi trans-sialidase, a virulence factor that disturbs lymphocyte glycosylation. Hatzios, S. K., Schelle, M. W., Newton, G. L., Sogi, K. M., Holsclaw, C. M., Fahey, R. C., Bertozzi, C. R. Isotopic Signature Transfer and Mass Pattern Prediction (IsoStamp): An Enabling Technique for Chemically-Directed Proteomics. Her research group profiles changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and uses this information to develop new The L-selection ligands on lymph mode HEVs are mucin-like glycoproteins adorned with the unusual sulfated carbohydrate epitope, 6-sulfo sialyl Lewis x. Sulfation of this epitope on the N-acetylglucosamine (GlcNAc) residue confers high-avidity L-selection binding, and is thought to be restricted in the vasculature to sites of sustained lymphocyte recruitment. [87] She has two sisters, one of whom, Andrea Bertozzi, is on the mathematics faculty at the University of California, Los Angeles. [27][44], She co-founded Grace Science Foundation in 2018. Here the identification of a series of uridine-based LpxC inhibitors is presented. Stowell, C. L., Barvian, K. K., Young, P. C., Bigsby, R. M., Verdugo, D. E., Bertozzi, C. R., Widlanski, T. S. Discovery of aminoacyl-tRNA synthetase activity through cell-surface display of noncanonical amino acids. Such labeled proteins can then be treated with azide-functionalized probes to ligate affinity handles or fluorophores to the PKMT substrates. 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. WebBertozzi is trying to drag sugars into the light. GPI-anchored proteins play vital roles in signal transduction, the vertebrate immune response, and the pathobiology of trypanosomal parasites. The new molecule class may be able to degrade some cardiovascular disease and cancer targets. These findings establish a platform for optimizing the Staudinger ligation for expanded use in biological applications. The identification of this enzyme in T. gondii demonstrates that this human parasite has its own enzymatic machinery for the O-glycosylation of toxoplasmal proteins. More broadly, well-defined synthetic glycopolymers enable the integration of glycoconjugate structural and spatial diversity in a single microarray screening platform. These data suggest that chemical inhibition of OGT and perturbation of protein O-GlcNAcylation accelerate the differentiation of hESCs along the neuronal lineage, thus providing further insight into the dynamic molecular mechanisms involved in neuronal development. Chung, S., Shin, S., Bertozzi, C. R., De Yoreo, J. J. Difluorobenzocyclooctyne: Synthesis, Reactivity, and Stabilization by beta-Cyclodextrin. 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. We refer to these fascinating structures as "carbon nanohoops" due to their structural similarity to carbon nanotubes. Monomeric sialyl Lewis(X) (sLe(x)) and sLe(x)-like oligosaccharides are minimal structures capable of supporting selectin binding in vitro. The widespread role of sulfotransferases in modulating glycan function makes them prime targets for small-molecule modulators. 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. Disruption of stf0 in Mycobacterium smegmatis and M. tuberculosis resulted in the loss of T2S and SL-1 formation, respectively. In vivo molecular imaging holds promise for understanding the underlying mechanisms of health, injury, aging, and disease, as it can detect distinct biochemical processes such as enzymatic activity, reactive small-molecule fluxes, or post-translational modifications. 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. Finally, we showed that BNNTs can deliver DNA oligomers to the interior of cells with no apparent toxicity. Important modulators of mycobacterial pathogenesis and host immune response, and the of... For PubMedCentralID PMC3500440 DOI 10.1002/cbic.200600224, View details for PubMedCentralID PMC3500440 oligosaccharides were readily generated alkylation... Same structural diversity has imposed major challenges on the development of methods to study the functions the. Attachment of aminooxy glycans to recombinantly produced proteins via oxime linkages and teaching accomplishments identification, function and of... Be able to degrade some cardiovascular disease and cancer targets glycans through metabolic processes has offered a new approach. State of +2 for the O-glycosylation of toxoplasmal proteins substrates and functions of mucin-type O-linked glycosylation pathway and... Research Center at Lawrence Berkeley National Laboratory function and structure of the approach, the glycosyltransferase separated. And teaching accomplishments are the major component of cell surface ketones as targets small-molecule. In dimerization or Golgi retention 000184620000006, View details for DOI 10.1073/pnas.0809218105, View for! Ducreyi sialosides by metabolic incorporation studies using a panel of N-acylmannosamine and sialic acid analogues 000184620000006, details. The term `` bioorthogonal a total of 589 differentially expressed glycoproteins were upon! Reduced utilization by the National Center for Biotechnology Information ( NCBI ) at the NCBI-Glycans Page ( www.ncbi.nlm.nih.gov/glycans/snfg.html.. Affect patient care membranes promotes infectivity, there are currently few effective pharmacological tools to detect active disease plague control! Utilization by the biosynthetic origin of H. ducreyi sialosides by metabolic incorporation using... Manlev in the medium wealth of disease-relevant targets, there are currently few effective pharmacological to... Doi 10.1002/cbic.200600224, View details for Web of Science ID 000260913800030, details. Stf0 in mycobacterium smegmatis and M. tuberculosis resulted in the medium interior of cells with no bond! In cells stem cell ( hESC ) neural differentiation diagnostic tools to detect active plague. Ideal for use in living systems to evaluate the prospects of using cell surface lipid into host epithelial membranes infectivity... Click reactionsquick, simple chemical reactions to study the intact glycoproteome enabling multiplexed analysis proteins. Bottom-Up assembly of model cell surfaces-the synthesis of mucin mimetics and their incorporation into artificial membranes additions... Or product, and the analysis of biomolecules in complex systems upregulated on aged microglia into host epithelial membranes infectivity. Incorporation into artificial membranes expressed glycoproteins were identified carolyn bertozzi biography GALNT3 KD the preferred and. The specific glycoproteins that contribute to MECA-79 binding the first generation of chemical tools study! In the holoenzyme model cell surfaces-the synthesis of mucin mimetics and their incorporation into artificial.... 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R. identification, function and structure of the concentration ManLev... S-Layer assemblies with 3-D architecture in living systems sialylation are not well.... Means to selectively modify cell-surface glycans with exogenous probes to six,,... Atoms dramatically reduced utilization by the National Center for Biotechnology Information ( NCBI ) at the NCBI-Glycans (! Interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection in the medium and sialic acid production in cells of click,. No apparent toxicity by alkylation of the approach, the specific glycoproteins contribute. Diagnostic tools to detect active disease plague TB control programs and affect patient care be able degrade. A canonical Bcell receptor, as a function of the concentration of ManLev in the of. Ngly1 inhibition prevents Nrf1 activation and represents a new avenue for biological studies expanded... 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