Cotton Medal for Excellence in Chemical Research, This page was last edited on 1 March 2023, at 21:09. View details for DOI 10.1074/mcp.M600314-MCP200, View details for Web of Science ID 000242852000012. Traditional chemical synthesis does not lend itself to the easy, rapid construction of even moderately sized biomolecules, because it requires elaborate protection schemes. Synthetic oligosaccharides and glycoconjugates provide materials for correlating structure with function. However, because they are internalized within hours, these glycopolymers could not be employed to probe processes that occur on longer time scales. View details for DOI 10.1371/journal.pone.0242049. The ligation exploits the bioorthogonal reaction of aldehydes and alkoxyamines to form an intermediate oxyiminium ion; this intermediate undergoes intramolecular C-C bond formation with an indole nucleophile to form an oxacarboline product that is hydrolytically stable. The approach exploits the requirement of Golgi localization, a common feature of glycosyltransferase superfamily members. Beam-type collisional activation, i.e., higher-energy collisional dissociation (HCD), has been a valuable approach, but stepped collision energy HCD (sceHCD) and electron transfer dissociation with HCD supplemental activation (EThcD) have emerged as potentially more suitable alternatives. Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans. We report that mycobacteria and other corynebacteria can be specifically detected with a fluorogenic trehalose analog. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. View details for Web of Science ID 000311072900014, View details for PubMedCentralID PMC3500440. A. Sequential assembly of the septal cell envelope prior to V snapping in Corynebacterium glutamicum. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. WebPrincipal Investigator. This story was updated on Wednesday, Oct. 6, at 1:23 p.m. PDT. View details for DOI 10.1002/anie.201508783, View details for PubMedCentralID PMC4736730, View details for Web of Science ID 000368061800025, View details for DOI 10.1093/glycob/cwv091, View details for PubMedCentralID PMC4643639, View details for DOI 10.1021/acscentsci.5b00336, View details for PubMedCentralID PMC4827536, View details for DOI 10.1073/pnas.1516127112, View details for DOI 10.1021/acscentsci.5b00301, View details for PubMedCentralID PMC4827521. Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. View details for Web of Science ID 000167618700043. 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 describe the computation-guided rational design of a cysteine- and lysine-containing 11-residue peptide sequence that reacts with 2-cyanobenzothiazole (CBT) derivatives. However, the synthetic difficulties inherent to sialylated and fucosylated oligosaccharides motivate the search for alternative antagonists. Furthermore, the same junctional peptidoglycan also serves as a mechanical link holding the daughter cells together and undergoes mechanical fracture during V snapping. View details for Web of Science ID 000177297600001. This study reports the vaccine potential of an attenuated 5'-adenosine phosphosulfate reductase mutant (DeltacysH) of M. tuberculosis. Importantly, glycopolymers containing biologically relevant branched oligosaccharides, such as sialyl Lewis(x), as well as sulfated glycosaminoglycan-like epitopes can be readily prepared using our methodology. PCL-1 is a boronic acid-caged firefly luciferin molecule that selectively reacts with H(2)O(2) to release firefly luciferin, which triggers a bioluminescent response in the presence of firefly luciferase. Bhat, R., Belardi, B., Mori, H., Kuo, P., Tam, A., Hines, W. C., Quynh-Thu Le, Q. T., Bertozzi, C. R., Bissell, M. J. In the mouse genome we have found a homologous ORF that predicts a novel murine GlcNAc 6-O-sulfotransferase with 88% identity to the human enzyme. de Almeida, G., Townsend, L. C., Bertozzi, C. R. Mycobacterium tuberculosis Rv3406 Is a Type II Alkyl Sulfatase Capable of Sulfate Scavenging. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of ADC toxicity. She is an elected member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the German Academy of Sciences Leopoldina. View details for Web of Science ID 000263320900008, View details for PubMedCentralID PMC2709987. Cell-surface glycans are attractive targets for molecule imaging due to their reflection of cellular processes associated with development and disease progression. During Bertozzi's third year of graduate school, Bednarski was diagnosed with colon cancer, which resulted in him taking a leave of absence and changing his career path by enrolling in medical school. Van de Bittner, G. C., Bertozzi, C. R., Chang, C. J. The key building block was a 2-azido-3-thiogalactose-Thr analogue that was incorporated into a peptide by fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. The formylglycine-generating enzyme (FGE) is required for the posttranslational activation of type I sulfatases by oxidation of an active-site cysteine to Calpha-formylglycine. Zurich (2009); Harrison Howe Award (2009); W. H. Nichols Award (2009); Willard Gibbs Medal (2008); Elected member of the German Academy of Sciences Leopoldina (2008); Roy L. Whistler International Award in Carbohydrate Chemistry (2008); Li Ka Shing Women in Science Award (2008); Ernst Schering Prize (2007); Elected member of the National Academy of Sciences (2005); T.Z. These results establish cell-surface glycoproteomics as an effective technique for discovery of cancer biomarkers. View details for DOI 10.1073/pnas.0437851100, View details for Web of Science ID 000181675200023, View details for PubMedCentralID PMC152251. Here, we report the development of antibody-sialidase conjugates that enhance tumor cell susceptibility to antibody-dependent cell-mediated cytotoxicity (ADCC) by selective desialylation of the tumor cell glycocalyx. Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Promote and support the Department of Chemistry. 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. We employed Tmp-SLF to modulate gene expression in a yeast three-hybrid assay. Transposon-sequencing was then used to define its essential gene set and identify loci that, when inactivated, confer hypersensitivity to ethambutol (EMB), a drug that targets AG biogenesis. To elucidate the important sites of sulfation on Le(x) with respect to L-selectin recognition, we have synthesized six sulfated Le(x) analogs and determined their abilities to block binding of a recombinant L-selectin-Ig chimera to immobilized GlyCAM-1. We envision that the attributes of this improved HIV OF assay can increase testing rates of at-risk individuals while enabling diagnosis and treatment at an earlier time point. Nijmegen) (2013); Elected Fellow of the National Academy of Inventors (2013); Heinrich Wieland Prize (2012); Elected member of the Institute of Medicine (2011); Tetrahedron Young Investigator Award for Bioorganic and Medicinal Chemistry (2011); Royal Society of Chemistry - Organic Division, Bioorganic Chemistry Award (2010); Lemelson-MIT Prize (2010); Albert Hofmann Medal, Univ. Delaveris, C. S., Chiu, S. H., Riley, N. M., Bertozzi, C. R. The clinical impact of glycobiology: targeting selectins, Siglecs and mammalian glycans. After injection of mice with a peracetylated form of GalNAz, azide-labeled glycoproteins were observed in a variety of tissues, including liver, kidney, and heart, in serum, and on isolated splenocytes. The compounds did not inhibit other mammalian glycosyltransferases or nucleotide sugar utilizing enzymes, suggesting selectivity for the ppGalNAcTs. In addition, alterations in mucin expression and glycosylation are common in a variety of human diseases, such as cancer, cystic fibrosis, and inflammatory bowel diseases. These values and the mathematical model confirm that chemoselective reactions on the cell surface can deliver to cells similar numbers of molecules as antibodies. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in Mycobacterium smegmatis results in distinct host immune responses. It deftly subverts the bactericidal mechanisms of alveolar macrophages, ultimately inducing granuloma formation and establishing long-term residence in the host. Alternatively, selective inhibition or activation of glycosyltransferases or glycosidases can define the biological roles of the corresponding glycans. The purified enzyme catalyzed the sequential esterification of trehalose with two palmitoyl groups, generating a diacylated product similar to the 2,3-diacyltrehalose glycolipids of M. tuberculosis. While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. An inhibitor of the UDP-GlcNAc 4-epimerase that synthesizes UDP-GalNAc, the donor initiating O-linked glycosylation, would be a powerful reagent for reversibly inhibiting O-linked glycosylation. Trypanosoma cruzi, the agent of the American trypanosomiasis or Chagas disease, bypasses its lack of de novo synthesis of sialic acids by expressing a surface-anchored trans-sialidase. Flynn, R. A., Belk, J. This was confirmed by enzymatic assay of the partially purified enzyme with unnatural substrates. GlcNAc6ST-2 is a member of a family of related enzymes that act on similar carbohydrate substrates in vitro but discrete glycoproteins in vivo. She is an elected member of the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells. We also exploited this finding to protect allogeneic and xenogeneic primary cells from NK-mediated killing, suggesting the potential of Siglecs as therapeutic targets in cell transplant therapy. 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