carolyn bertozzi biography

Unnatural analogues of sialic acid can be delivered to mammalian cell surfaces through the metabolic transformation of unnatural N-acetylmannosamine (ManNAc) derivatives. Mucin-type O-glycans could be imaged as early as 7 hours postfertilization, during the gastrula stage of development. We report herein the chemical synthesis and preliminary mechanistic investigation of diptericin, an 82 residue glycopeptide that contains regions similar to two different types of antibacterial peptides. Methods for targeting of small molecules to cellular proteins can allow imaging with fluorophores that are smaller, brighter, and more photostable than fluorescent proteins. Chang, P. V., Prescher, J. Miller, C. L., Sagiv-Barfi, I., Neuhfer, P., Czerwinski, D. K., Artandi, S. E., Bertozzi, C. R., Levy, R., Cochran, J. R. On-tissue spatially resolved glycoproteomics guided by N-glycan imaging reveal global dysregulation of canine glioma glycoproteomic landscape. Small molecule inhibitors of carbohydrate biosynthetic and processing enzymes can block the assembly of specific oligosaccharide structures. Delaveris, C. S., Webster, E. R., Banik, S. M., Boxer, S. G., Bertozzi, C. R. Introducing "In Focus", Community Resources Accelerating Science. She is also an Investigator at the Howard Hughes Medical Institute (HHMI) and is the former Director of the Molecular Foundry. Drake, P. M., Stock, C. M., Nathan, J. K., Gip, P., Golden, K. P., Weinhold, B., Gerardy-Schahn, R., Bertozzi, C. R. Selective Enrichment of Azide-Containing Peptides from Complex Mixtures. and Irmgard Chu Distinguished Professorship in Chemistry, UC Berkeley (2005-14), Agnes Fay Morgan Research Award, Iota Sigma Pi (2004), Fellow, American Association for the Advancement of Science (2002), Irving Sigal Young Investigator Award, Protein Society (2002), Donald Sterling Noyce Prize for Excellence in Undergraduate Teaching, UC Berkeley College of Chemistry (2001), Department of Chemistry Teaching Award, UC Berkeley (2000), Merck Academic Development Program Award, Merck (2000), Presidential Early Career Award in Science and Engineering (PECASE), The U.S. White House (2000), Camille Dreyfus Teacher-Scholar Award, Camille and Henry Dreyfus Foundation (1999), Beckman Young Investigator Award, Arnold and Mabel Beckman Foundation (1998), Glaxo Wellcome Scholar, Glaxo Wellcome (1998), Prytanean Faculty Award, Prytanean Women's Honor Society, UC Berkeley (1998), Research Innovation Award, Research Corporation (1998), Young Investigator Award, Office of Naval Research (1998), Horace S. Isbell Award in Carbohydrate Chemistry, American Chemical Society (1997), New Investigator Award in Pharmacology, Burroughs Wellcome (1997), Sloan Research Fellow, Alfred P. Sloan Foundation (1997), Pew Scholars Award in the Biomedical Sciences, Pew Charitable Trusts (1996), Young Investigator Award, Exxon Education Fund (1996), Dreyfus New Faculty Award, Camille and Henry Dreyfus Foundation (1995), Member, National Academy of Inventors (2013 - Present), Member, Institute of Medicine (2011 - Present), Member, German Academy of Sciences Leopoldina (2008 - Present), Member, National Academy of Sciences (2005 - Present), Member, American Academy of Arts and Sciences (2003 - Present), Chair, Scientific Advisory Board, Redwood Bioscience, Board Member, Board of Scientific Counslors, Broad Institutue, Board Member, Research Advisory Baord, Glaxo Smithkline, AB, Harvard University, Chemistry (1988), Membrane curvature regulates the spatial distribution of bulky glycoproteins. The tremendous selectivity of the transformation should permit its execution within a cell's interior, offering new possibilities for probing intracellular interactions. Individuals with GeneXpert-positive pulmonary TB were sampled pre-treatment over 60-minutes. Finally, we found that metabolic labeling of both cell envelope structures reports on drug effects on cell physiology in two hours, far faster than a genetic sensor of cell envelope stress. Lemieux, G. A., de Graffenried, C. L., Bertozzi, C. R. Metabolic incorporation of unnatural sialic acids into Haemophilus ducreyi lipooligosaccharides. A., Bertozzi, C. R. Extensive Determination of Glycan Heterogeneity Reveals an Unusual Abundance of High Mannose Glycans in Enriched Plasma Membranes of Human Embryonic Stem Cells. Both significantly outperform EThcD methods, indicating that ETD-based methods are not required for routine N-glycoproteomics. She is known for creating the term "bioorthogonal chemistry" for chemical reactions with living systems. Co-opting cellular factors for viral translation and viral genome replication at the endoplasmic reticulum is a shared replication strategy, despite different clinical outcomes. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" 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. Complete assignment of all (1)H and (13)C resonances in the spectra of these deoxytrehaloses was achieved through the extensive use of 2D [(1)H,(1)H] and [(1)H,(13)C] correlation NMR experiments. The azido sugars are then covalently tagged, either ex vivo or in vivo, using one of two azide-specific chemistries: the Staudinger ligation, or the strain-promoted [3+2] cycloaddition. Both ordered tetrameric states emerge from clusters of the monomer phase, however, they then track along two different pathways. 1-68A and a 2-dehydroxy analogue, 1-68Aa, inhibit several purified LpxC orthologues. 5 '-adenosinephosphosulfate lies at a metabolic branch point in mycobacteria. This unique technique is currently being used to investigate the enzymatic mechanism of NodST and to identify sulfotransferase inhibitors. Likewise, these crosslinking probes serve as ideal chemical tools for structural studies between NRPS modules where functional assays are lacking. However, their diverse structures, which are the key to their function, have hampered studies by biologists and chemists alike. UDP-GlcNAc 2-epimerase and GlcNAc 2-epimerase are two enzymes capable of generating ManNAc from UDP-GlcNAc and GlcNAc, respectively. No BPAS is found inside the cells. View details for DOI 10.1073/pnas.0911247107, View details for Web of Science ID 000275131100011, View details for PubMedCentralID PMC2840165. Sogi, K. M., Gartner, Z. J., Breidenbach, M. A., Appel, M. J., Schelle, M. W., Bertozzi, C. R. Self-Assembly of "S-Bilayers", a Step Toward Expanding the Dimensionality of S-Layer Assemblies. The obtained data also uncover numerous novel glycoproteins; some of which could represent new potential EOC biomarkers and/or therapeutic targets. This structure suggests a molecular mechanism by which conserved G domain architecture is used to energetically link GTP turnover to the production of an essential metabolite. The immobilization procedure itself was found not to activate primary T-cells, in contrast to previously reported antibody- and lectin-based methods. A., Bertozzi, C. R. Fluorophore Targeting to Cellular Proteins via Enzyme-Mediated Azide Ligation and Strain-Promoted Cycloaddition. 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). The Leu-13 --> Gly (L13G) mutation is found in each of the three MetRS mutants, and the MetRS variant containing this single mutation is highly efficient in producing recombinant proteins that contain azidonorleucine. The polymers were designed to mimic native cell-surface mucin glycoproteins, which are defined by their dense glycosylation patterns and rod-like structures. A ligation modeled after the Staudinger reaction forms an amide bond by coupling of an azide and a specifically engineered triarylphosphine. Bertozzi, C. R., SINGER, M. S., ROSEN, S. D. L-selectin-carbohydrate interactions: Relevant modifications of the Lewis x trisaccharide. Mycobacterium tuberculosis (M. tuberculosis) is an intracellular pathogen possessing a complex mixture of cell wall lipids that are thought to modulate the activities of host macrophages. A novel germline variant in CSF3R reduces N-glycosylation and exerts potent oncogenic effects in leukemia. Although global sulfatase activity was reduced in the mutant, a significant amount of residual sulfatase activity suggests the presence of FGE-independent sulfatases in this organism. Cyclodextrin complexation is therefore a promising approach for stabilizing compounds that possess the high intrinsic reactivities desired for Cu-free click chemistry. 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. An undecasaccharide mimetic was then readily generated by alkylation of this glycopeptide with an N-bromoacetamido trisaccharide. Furthermore, the study of SL-1 has led to questions regarding the significance of sulfation in mycobacteria. 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 provide evidence that conserved switch motifs in the G domain of CysN allosterically mediate interactions between the nucleotide binding sites. The presence of SiaLev groups on the neuronal cell surface did not impede neurite outgrowth or significantly affect the distribution of PSA on neuronal compartments. 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. The second-order rate constant for PAP was determined to be over 3 orders of magnitude greater than those determined for myo-inositol 1-phosphate (IMP) and fructose 1,6-bisphosphate (FBP), previously considered to be the primary substrates of this enzyme. The selectins are a family of three adhesion molecules (L-, P-, and E-) that direct the interaction of circulating leukocytes with endothelial cells during the first step in recruitment to tissue sites. Both normal and cancerous prostate tissues were sliced and cultured in the presence of the azide-functionalized sialic acid biosynthetic precursor Ac4 ManNAz. ( Bertozzi Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. Phosphorylation of Rv0516c regulated the abundance of EspA, a virulence-associated substrate of the type VII ESX-1 secretion system. These measurements show that the glycocalyx exhibits nanoscale organization on both cell lines and primary human tumor cells. Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. Our data show that over 50% of O-glycopeptides in our sample generated from combined digestion using OpeRATOR and trypsin contain multiple O-glycosites, indicating that collision-based fragmentation alone is not sufficient. Finally, using StcE, we discovered that sialic acid-binding Ig-type lectin-7 (Siglec-7), a glycoimmune checkpoint receptor, selectively binds sialomucins as biological ligands, whereas the related receptor Siglec-9 does not. Specific glycocalyx compositions can also induce plasma membrane instabilities to generate more exotic undulating and pearled membrane structures and drive secretion of extracellular vesicles. View details for Web of Science ID 000168490400007, View details for Web of Science ID 000167717100191. View details for DOI 10.1074/jbc.M510520200, View details for Web of Science ID 000235426200035. 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. DMN-Tre labeling enabled the rapid, no-wash visualization of mycobacterial and corynebacterial species without nonspecific labeling of Gram-positive or Gram-negative bacteria. P. aeruginosa APS reductase contains an [4Fe-4S] cluster that is essential for catalysis. 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. O-Glycosylation affects relatively minor components of cell surfaces. Mutations in the colony stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as AML. 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. Shurer, C. R., Kuo, J. C., Roberts, L. M., Gandhi, J. G., Colville, M. J., Enoki, T. A., Pan, H., Su, J., Noble, J. M., Hollander, M. J., O'Donnell, J. P., Yin, R., Pedram, K., Mockl, L., Kourkoutis, L. F., Moerner, W. E., Bertozzi, C. R., Feigenson, G. W., Reesink, H. L., Paszek, M. J. CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. This technique causes no discernible membrane or cell damage, and can deliver a discrete number of molecules to the cell's interior without the requirement of a carrier solvent. An N-azidoacetylmannosamine derivative caged with a peptide substrate for the prostate-specific antigen (PSA) protease was converted to cell-surface azido sialic acids in a PSA-dependent manner. We present a novel glycodendron prosthetic which can be site-selectively appended to recombinant proteins to create 'N-glycosylated' glycoprotein mimics. Shui, W., Gilmore, S. A., Sheu, L., Liu, J., Keasling, J. D., Bertozzi, C. R. Synthesis, Characterization, and Theory of [9]-, [12]-, and [18]Cycloparaphenylene: Carbon Nanohoop Structures. Our editors will review what youve submitted and determine whether to revise the article. Baker Family Director of Stanford ChEM-H, Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences and Professor, by courtesy, of Chemical and Systems Biology and of Radiology, AB, Harvard University, Chemistry (1988). The unsymmetrical (2'-, 3'-, 4'- and 6'-) monodeoxy analogs were synthesized by desymmetrization of alpha,alpha-trehalose and subsequent deoxygenation under radical conditions. Cells are modified with membrane-bound single-stranded DNA, and specific single-cell capture is directed by the complementary strand bound in the sensor area of the iridium oxide pH microelectrodes within a microfluidic channel. These studies establish Cu-free click chemistry as a bioorthogonal reaction that can be executed in the physiologically relevant context of a mouse. Here, we describe the computation-guided rational design of a cysteine- and lysine-containing 11-residue peptide sequence that reacts with 2-cyanobenzothiazole (CBT) derivatives. Gordon, C. G., Mackey, J. L., Jewett, J. C., Sletten, E. M., Houk, K. N., Bertozzi, C. R. Mapping Yeast N-Glycosites with Isotopically Recoded Glycans. Lantos, A. Bowman, K. G., Cook, B. N., de Graffenried, C. L., Bertozzi, C. R. The evolving academic research environment, Chemical synthesis of lymphotactin: A glycosylated chemokine with a C-terminal mucin-like domain. The difference in preferred substrates between L-selectin and MECA-79 may explain the variable activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial venules in lymphoid organs. Members of the selectin family of adhesion receptors, consisting of L-, P- and E-selectin, mediate the initial interaction between leukocytes and endothelium during leukocyte trafficking from the blood into tissue sites. View details for DOI 10.1021/acscentsci.6b00382, View details for PubMedCentralID PMC5200921. View details for Web of Science ID 000237590400012. The key building block, a pentasaccharide-Asn analogue containing two thiol residues, was incorporated into CD52 by 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. View details for Web of Science ID 000321093800027. Here we describe a biarylazacyclooctynone (BARAC) that has exceptional reaction kinetics and whose synthesis is designed to be both modular and scalable. Genomic and proteomic profiling form a basis for biological discovery. Glycoproteins are typically expressed as mixtures of glycoforms, their oligosaccharides being generated by a template-independent biosynthetic process. Recently, the ability to modify monosaccharide structures within cellular glycans through metabolic processes has offered a new avenue for biological studies. Additionally, we demonstrate that in C. glutamicum, the peripheral peptidoglycan layer at the septal junction remains contiguous throughout septation, forming a diffusion barrier for the fluid mycomembrane. Their function, have hampered studies by biologists and chemists alike as early as 7 hours,. Undecasaccharide mimetic was then readily generated by a template-independent biosynthetic process 1-68Aa, inhibit several purified orthologues..., M. 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Oligosaccharides being generated by a template-independent biosynthetic process residing on the cell surface are of interest! Rv0516C regulated the abundance of EspA, a virulence-associated substrate of the Molecular Foundry biologists chemists! Some of which could represent new potential EOC biomarkers and/or therapeutic targets by coupling of an Azide and specifically! Promising approach for stabilizing compounds that possess the high intrinsic reactivities desired for click. Cell surface are of particular interest in biotherapeutics create ' N-glycosylated ' glycoprotein mimics inducers... And/Or therapeutic targets of EspA, a virulence-associated substrate of the Lewis x trisaccharide its within. Reaction kinetics and whose synthesis is designed to mimic native cell-surface mucin glycoproteins, and those residing the!