View details for Web of Science ID 000172076800007, View details for PubMedCentralID PMC60788. WebCarolyn Ruth Bertozzi is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. Bifunctional, fluorinated cyclooctynes were used for the in situ "click" crosslinking of azide-terminated photodegradable star polymers, yielding photodegradable polymeric model networks with well-defined structures and tunable gelation times. Glycan structural diversity is directly correlated with difficulty in characterizing the intact glycoproteome by mass spectrometry (MS). Conceptual translation of the cDNA sequence reveals a relatively long (i.e. Surprisingly, for three of the enzymes, significant activity was observed with sialylated LacNAc, and two of the enzymes were capable of detectable sulfation of GlcNAc in the context of sialyl Lewis x. Although the mechanisms of Golgi enzyme localisation are still under debate, the distribution of these enzymes among the Golgi cisternae can dictate the overall structures produced by the cell. We observed crosslinking between FG-repeat nucleoporins and nuclear transport factors, suggesting that O-GlcNAc residues are intimately associated with essential recognition events in nuclear transport. 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. Here we describe an approach for probing the galectin-induced multimerization of glycoconjugates on cultured cells. We chemically fused a recombinant sialidase to the human epidermal growth factor receptor 2 (HER2)-specific antibody trastuzumab through a C-terminal aldehyde tag. We have therefore made use of recently developed synthetic mucin mimetics, in which the core alpha-GalNAc monosaccharides of natural mucins are conjugated to a lipidated polymer backbone and anchored to fluid, solid-supported lipid membranes, and fluorescence interference contrast microscopy, an optical technique that provides nanometer-scale topographic information about objects near a reflective interface, to measure the orientation of the mucin mimics relative to the membrane plane. Pluvinage, J. V., Haney, M. S., Smith, B. This genetically encoded 'aldehyde tag' is no larger than a His(6) tag and can be exploited for numerous protein labeling applications. Protocol for cell type-specific labeling, enrichment, and proteomic profiling of plasma proteins in mice. Single-particle tracking was used to characterize the diffusion dynamics of injected quantum dots in the cytosol. Most progress has occurred in the area N-glycoproteomics. View details for Web of Science ID 000180258800025, View details for Web of Science ID 000181755600011, View details for Web of Science ID 000185102400018. Furthermore, Rv0516c disruption modified peptidoglycan thickness, enhanced antibiotic resistance, and activated genes in the regulon of the alternative -factor SigF. Although the early steps in SL-1 biosynthesis are known, the machinery underlying the final acylation reactions is not understood. [39], In 2014, she co-founded Enable Biosciences[27] of South San Francisco, California. Bertozzi holds the Anne T. and Robert M. Bass Professorship in the School of Humanities and Sciences at Stanford University. 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. Tian, E., Ten Hagen, K. G., SHUM, L., Hang, H. C., Imbert, Y., Young, W. W., Bertozzi, C. R., Tabak, L. A. The Staudinger ligation is highly selective and reliably forms its product in environs as demanding as live mice. These uridine analogs represent the first generation of chemical tools to study the functions of mucin-type O-linked glycosylation. Both reactive partners are abiotic and chemically orthogonal to native cellular components. This article contains raw and processed data related to research published in "Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation" [1]. 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. Upon exposure to mycobacterial cell wall lipids, 166 macrophage proteins showed differential expression. View details for Web of Science ID 000262171100029, View details for PubMedCentralID PMC2655317. Using an Orbitrap Fusion Tribrid mass spectrometer, we identified 699 intact glycopeptides from 192 glycoproteins. 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. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces unique sulfated metabolites associated with virulence. Sogi, K. M., Holsclaw, C. M., Fragiadakis, G. K., Nomura, D. K., Leary, J. Here we report that H. ducreyi can use unnatural sialic acids bearing elongated N-acyl groups from three to seven carbon atoms in length, resulting in outer membrane presentation of unnatural sialyl-LOS. Herein we describe a novel glycosyltransferase assay that exploits their unnatural substrate tolerance and the unique chemical reactivity of the azide. Hotsclaw, C. M., Sogi, K. M., Gilmore, S. A., Scheller, M. W., Leavell, M. D., Bertozzi, C. R., Leary, J. Here we highlight chemical tools that are beginning to address this need. SL-1 consists of a trehalose-2-sulfate (T2S) disaccharide elaborated with four lipids. Here we report that a bulky glycocalyx promotes the expansion of disseminated tumor cells in vivo by fostering integrin adhesion assembly to permit G1 cell cycle progression. Finally, the lipase inhibitor tetrahydrolipstatin disrupts Chp1 activity in M. tuberculosis, suggesting an avenue for perturbing SL-1 biosynthesis in vivo. Yet, our understanding of the invivo ligands and function for most lectins is still incomplete. View details for DOI 10.1074/jbc.M304928200, View details for Web of Science ID 000185713800121. We describe a metabolism-based approach to the selection of mutants in glycoconjugate biosynthesis that provides insight into regulatory mechanisms for oligosaccharide expression and metabolic flux. These receptors have attracted great attention in recent years due to their participation in a number of acute and chronic inflammatory diseases. Disruption of stf0 in Mycobacterium smegmatis and M. tuberculosis resulted in the loss of T2S and SL-1 formation, respectively. Using this approach, we identify 133 N-glycosites spanning 58 proteins, nearly doubling the number of experimentally observed N-glycosites in the yeast proteome. These results demonstrate the design of macromolecules with specific orientational preferences, as well as nanometer-scale measurement of their orientation. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. We have found that TDM monolayers, in stark contrast to phospholipid membranes, can be dehydrated and rehydrated without loss of integrity, as assessed by fluidity and protein binding. To address this deficiency, chemists have developed technologies to perturb glycan biosynthesis, profile their presentation at the systems level, and perceive their spatial distribution. Screening of the library identified an inhibitor with a K(i) value of 11 microM. Treatment of hESCs with Ac4-5SGlcNAc during induction limited protein O-GlcNAcylation and also caused a dramatic decrease in global levels of UDP-GlcNAc. Malaker, S. A., Shon, J., Pedram, K., Riley, N. M., Bertozzi, C. R. AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. An RNA-centric dissection of host complexes controlling flavivirus infection. Incorporation of sialosides into LOS was assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry. 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. WebBio. We identify and characterize C18ORF8/RMC1 as a regulator of ADC toxicity through its role in endosomal maturation. The glycosylated polymers were end-functionalized with lipid groups and embedded into supported lipid bilayers where they interact with protein receptors in a structure-dependent manner. Poor diagnostic tools to detect active disease plague TB control programs and affect patient care. Here we demonstrate that the Staudinger ligation can be executed in living animals, enabling the chemical modification of cells within their native environment. View details for Web of Science ID 000255629400034, View details for PubMedCentralID PMC2724873. Z. Multi-omics analysis of spatially distinct stromal cells reveals tumor-induced O-glycosylation of the CDK4-pRB axis in fibroblasts at the invasive tumor edge. Polysialyltransferases catalyze the glycosylation of the neural cell adhesion molecule (NCAM) with polysialic acid (PSA). Such genetic engineering in combination with stable isotopic labeling can be applied to various metabolic pathways and their products. After completing postdoctoral work at UCSF in the field of cellular immunology, she joined the UC Berkeley faculty in 1996. New therapies are therefore needed to treat diseases caused by these organisms, and a better understanding of the mechanisms of envelope assembly should aid in their discovery. View details for DOI 10.1021/acs.chemrev.6b00023, View details for Web of Science ID 000389962700001, View details for PubMedCentralID PMC5327817, View details for DOI 10.1021/acscentsci.6b00341, View details for PubMedCentralID PMC5126708. IsoTaG is therefore positioned to enhance structural understanding of the glycoproteome. We synthesized two unnatural oligosaccharide substrates, GlcNAc beta 1-->6Gal alpha-R and Gal beta 1-->4GlcNAc beta 1-->6Gal alpha-R, that incorporate structural motifs from the native L-selection ligands into an unnatural C-glycosyl hydrocarbon scaffold. Northern blot analysis identified a single 5.5-kb ppGalNAc-T transcript. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of ADC toxicity. Stanford, CA 94305Phone: (650) 723-2501Campus Map, UndergraduatesPh.D. We previously established that mouse multipotent hematopoietic progenitors use ST8Sia IV to express polySia on their cell surfaces. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Cross-linked polymethacrylamide and polymethacrylate hydrogels were functionalized with mineral-binding ligands and used to template the formation of hydroxyapatite. Here we describe a method for the site-specific introduction of aldehyde groups into recombinant proteins using the 6-amino-acid consensus sequence recognized by the formylglycine-generating enzyme. We have demonstrated that the quadricyclane ligation is compatible with, and orthogonal to, strain-promoted azide-alkyne cycloaddition and oxime ligation chemistries by performing all three reactions in one pot on differentially functionalized protein substrates. [89][90][91], Bertozzi is a lesbian and has been out since the late 1980s. de Almeida, G., Townsend, L. C., Bertozzi, C. R. Mycobacterium tuberculosis Rv3406 Is a Type II Alkyl Sulfatase Capable of Sulfate Scavenging. These findings provide a platform for defining the molecular basis of SMK's role in M. tuberculosis pathogenesis. The alkyl azide was then selectively derivatized with cyclo-octyne conjugates to various probes. A RECEPTOR-MEDIATED IMMUNE-RESPONSE USING SYNTHETIC GLYCOCONJUGATES, THE SYNTHESIS OF 2-AZIDO C-GLYCOSYL SUGARS, ANTIBODY TARGETING TO BACTERIAL-CELLS USING RECEPTOR-SPECIFIC LIGANDS, AN EFFICIENT METHOD FOR THE SYNTHESIS OF ALPHA-C-GLYCOSYL AND BETA-C-GLYCOSYL ALDEHYDES, THE SYNTHESIS OF HETEROBIFUNCTIONAL LINKERS FOR THE CONJUGATION OF LIGANDS TO MOLECULAR PROBES, COADSORPTION OF FERROCENE-TERMINATED AND UNSUBSTITUTED ALKANETHIOLS ON GOLD - ELECTROACTIVE SELF-ASSEMBLED MONOLAYERS. bertozzi@stanford.edu. A functional domain of the M. tuberculosis CysC protein was cloned and expressed in E. coli, confirming the ability of this organism to make PAPS. Laughlin, S. T., Agard, N. J., Baskin, J. M., Carrico, I. S., Chang, P. V., Ganguli, A. S., Hangauer, M. J., Lo, A., Prescher, J. Glycosylation is an essential form of post-translational modification that regulates intracellular and extracellular processes. WebDr. Mahal, L. K., Yarema, K. J., Bertozzi, C. R. 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