A., Boojamra, C. G., Griggs, J. L., Bertozzi, C. R. Tin-mediated phosphorylation: Synthesis and selectin binding of a phospho Lewis a analog. Pratt, M. R., Leigh, C. D., Bertozzi, C. R. A chemical approach for identifying O-GlcNAc-modified proteins in cells. The simplicity and generality of this method make it well suited for use in the study of carbohydrate-mediated cell surface interactions. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. A key feature of the synthesis was application of an intramolecular aglycon delivery reaction to join two differentially protected glucose monomers, one prepared with a novel alpha-selective glycosylation. Martin, D. D., Vilas, G. L., Prescher, J. Each enzyme preferred a terminal GlcNAc residue, and was impeded by the addition of a beta1,4-linked Gal residue (i.e., terminal LacNAc). 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. These values and the mathematical model confirm that chemoselective reactions on the cell surface can deliver to cells similar numbers of molecules as antibodies. Malaker, S. A., Pedram, K., Ferracane, M. J., Bensing, B. We report that cell surface PSA expression can be reversibly inhibited by a small molecule, N-butanoylmannosamine (ManBut). Azido sugars are fed to cells and integrated by the glycan biosynthetic machinery into various glycoconjugates. 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. Furthermore, we developed a biomemetic coating strategy to interface BNNTs with proteins and cells. Four recently discovered GlcNAc-6-sulfotransferases are the first candidate contributors to the biosynthesis of 6-sulfo sLex in the context of L-selectin ligands. 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. Using high-performance liquid chromatography, we quantified the degree of accumulation and reversibility upon acidic compartment neutralization in macrophages and observed that accumulation was greater in infected than in uninfected macrophages. The combination of novel biochemical and metabolism-based approaches with emerging genomic methods promises to accelerate efforts to understand glycosylation. A., Bertozzi, C. R., Marahiel, M. A., Burkart, M. D. Uridine-Based Inhibitors as New Leads for Antibiotics Targeting Escherichia coli LpxC. Chen, Q., Zhang, D., Somorjai, G., Bertozzi, C. R. Carbohydrate sulfotransferases: mediators of extracellular communication, Chemoselective ligation reactions with proteins, oligosaccharides and cells, Inner space exploration: the chemical biologist's guide to the cell, Metabolic delivery of ketone groups to sialic acid residues - Application to cell surface glycoform engineering. View details for DOI 10.1093/glycob/cwi064, View details for Web of Science ID 000230346400006. Mucin-type O-gly co sy la tion is initiated by a large family of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAc Ts) that transfer GalNAc from UDP-GalNAc to the Ser and Thr residues of polypeptide acceptors. A key tool in this study is the Staudinger ligation, a highly selective reaction between modified triarylphosphines and azides that produces an amide-linked product. The screening approach described here provides an integrated platform to identify specific modulators of palmitoylated proteins, demonstrated here for Ras and Fyn, but potentially applicable to pharmaceutical targets involved in a variety of human diseases. We describe here a new ELISA that measures the binding between selectin-IgG chimeras and a physiological ligand for L-selectin and can be used to screen selectin inhibitors. A., Bertozzi, C. R. Global gene expression of cells attached to a tissue engineering scaffold, Directing flux in glycan biosynthetic pathways with a small molecule switch. Furthermore, we determined that the PAT biosynthetic machinery has no cross-talk with that for sulfolipid-1 despite their related structures. 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. Although the polysialyltransferase ST8Sia IV is expressed in both primary and secondary human lymphoid organs, its product, polysialic acid (polySia), has been largely overlooked by immunologists. Mucin-type O-glycans could be imaged as early as 7 hours postfertilization, during the gastrula stage of development. Even though we have only demonstrated its use in visualizing glycans, it can be envisioned that this probe could also be used for bioluminescence imaging of any azide-containing biomolecule, such as proteins and lipids, since azides have been previously incorporated into these molecules. Because the parameters which govern this effect are well understood and are amenable to chemical modification, this knowledge may enable the rational development of more effective antibiotics against tuberculosis. These reactions possess extreme selectivity and biocompatibility, such that their participating reagents can form covalent bonds within richly functionalized biological systems--in some cases, living organisms. We show that Glyco-seek detects attomoles of glycoproteins of interest from cell lysates, with sensitivity several orders of magnitude higher than that of current techniques. Metabolic and bioorthogonal labeling methods have previously enabled the enrichment and identification of sialoglycoproteins from cultured cells and model organisms. View details for DOI 10.1016/j.bmcl.2011.05.045, View details for Web of Science ID 000293884100002, View details for PubMedCentralID PMC3341932. Factors including glycan heterogeneity, low abundance, and low occupancy can complicate site mapping. A novel and efficient enzyme kinetics assay using electrospray ionization mass spectrometry was developed and applied to the bacterial carbohydrate sulfotransferase (NodST). WebBio BIO Professor Carolyn Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface sugars important to human health and disease. In the first step of the pathway, APS reductase catalyzes the reduction of adenosine 5'-phosphosulfate (APS) to adenosine 5'-phosphate (AMP) and sulfite with reducing equivalents from the protein cofactor, thioredoxin. Chemical tools have proven indispensable for studies in glycobiology. View details for DOI 10.1016/j.molcel.2020.03.030. This phenomenon was first described in the early 1970s, but the molecular details underlying such transformations were poorly understood. View details for Web of Science ID 000232605600062. The Staudinger ligation has sufficient biocompatibility for performance in living animals but suffers from phosphine oxidation and synthetic challenges. Tsui, C. K., Barfield, R. M., Fischer, C. R., Morgens, D. W., Li, A., Smith, B. Members of the Corynebacterineae, including Corynebacterium and Mycobacterium, have an atypical cell envelope characterized by an additional mycomembrane outside of the peptidoglycan layer. We report the 2.7 A resolution crystal structure of Pseudomonas aeruginosa APS reductase in the thiosulfonate intermediate form of the catalytic cycle and with substrate bound. This Account summarizes chemoselective approaches for assembling homogeneous glycoconjugates that attempt to reduce the barriers to their synthesis. She is an elected member of the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. Application of our enzymatic toolkit to ascites fluid and tissue slices from patients with ovarian cancer facilitated characterization of patients based on differences in mucin cleavage and expression patterns. The unique chemical functionality of these analogs is exploited for selective attachment of singlet oxygen-generating fluorescent dyes via bioorthogonal 'click chemistry' ligations. 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. Dube, D. H., Prescher, J. Despite this wealth of disease-relevant targets, there are currently few effective pharmacological tools to interfere with protein palmitoylation. Erik Gregersen is a senior editor at Encyclopaedia Britannica, specializing in the physical sciences and technology. [8] Since 2021 she has been a member of the Accademia dei Lincei. Carol Bertozzi, a Stanford University chemist, won the Nobel Prize in chemistry in 2022. As with native mucins, the cell-surface display of CholA-anchored glycopolymers influenced the focal adhesion distribution. After subsequent injection with cyclooctyne reagents, glycoconjugate labeling was observed on isolated splenocytes and in a variety of tissues including the intestines, heart, and liver, with no apparent toxicity. The following reductive cleavage of the disulfide bonds within the cell's interior resulted in the release of cargo inside the cells, after which the nanoneedle was retracted by AFM control. This type of enzyme catalyzes the initial step of mucin-type O-glycosylation, that is, the transfer of GalNAc in O-glycosidic linkage to serine and threonine residues in polypeptides. Van de Bittner, G. C., Dubikovskaya, E. A., Bertozzi, C. R., Chang, C. J. We designed phosphine-luciferin reagent 1 to activate bioluminescence in response to Staudinger ligation with azide-labeled glycans. We used this technique to image fucosylated glycans in the enveloping layer of zebrafish embryos during the first 5 days of development. 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. 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. Despite recent progress, important mechanistic questions, such as the precise bacterial targets, the nature of any cooperation that occurs between peptides, and the purpose of multiple peptide isoforms, remain largely unanswered. Research into protein glycosylation, therefore, has benefited from homogeneous, structurally-defined glycoproteins obtained by chemical synthesis. Bittner, G. L., Prescher, J is a senior editor Encyclopaedia... Synthetic challenges complicate site mapping C., Dubikovskaya, E. A., Bertozzi, C. J been! 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