Here, we demonstrate that recombinant proteins expressed in mammalian cells can be site-specifically modified by using a genetically encoded aldehyde tag. 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. The leukocyte adhesion molecule L-selectin mediates lymphocyte homing to secondary lymphoid organs and to certain sites of inflammation. 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. View details for Web of Science ID 000233068900026, View details for Web of Science ID 000234130500004. We discuss the use of fluorescent and fluorogenic trehalose probes for the detection of the mycobacterial trehalose glycolipids. View details for Web of Science ID 000169081700029. While these lectins possess the ability to agglutinate A(1)-blood cells carrying the -GalNAc epitope and cross-link low valency glycoconjugates, only SBA showed a tendency to form intermolecular cross-links among the arrayed polyvalent mucin mimetics. Corrections? 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. [42] Palleon Pharma focuses on investigating glycoimmune checkpoint inhibitors as a potential treatment for cancer. Our results show that, like palmitate, incorporation of azido-palmitate occurred on mitochondrial proteins via thioester bonds at sites that could be competed out by palmitoyl-CoA. Using a panel of sulfated lactose (Galbeta1-->4Glc) neoglycolipids as substrates in direct binding assays, we found that 6',6-disulfolactose was the preferred structure for L-selectin, although significant binding to 6'- and 6-sulfolactose was observed as well. A., Dube, D. H., Bertozzi, C. R. Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis. Yap, M. C., Kostiuk, M. A., Martin, D. D., Perinpanayagam, M. A., Hak, P. G., Siddam, A., Majjigapu, J. R., Rajaiah, G., Keller, B. O., Prescher, J. She is the 50th American Cancer Society -funded researcher and the first woman researcher funded by ACS to win the prestigious honor. To identify a tagged-peptide's sequence, we performed an inclusion list-driven shotgun proteomics experiment where peptides bearing a recoded mass envelope were targeted for fragmentation, allowing for direct site mapping. Biography. The cognate ligands for L-selectin possess the unusual sulfated tetrasaccharide epitope 6-sulfo sialyl Lewis x (Siaalpha2-->3Galbeta1-->4[Fucalpha1-->3][SO(3)-->6]GlcNAc). View details for DOI 10.1073/pnas.0700567104, View details for Web of Science ID 000246599900007, View details for PubMedCentralID PMC1895932. Research on the human pathogen Mycobacterium tuberculosis (Mtb) would benefit from novel tools for regulated gene expression. Over time, the trapped state transforms into the stable state. We used this strategy to construct a paracrine signaling network in isolated 3-dimensional microtissues. Schilling, B., Goon, S., Samuels, N. M., Gaucher, S. P., Leary, J. For the glycopeptide substrates, ppGalNAc T10 exhibited a single large preference for Ser/Thr-O-GalNAc at the +1 (C-terminal) position relative to the Ser or Thr acceptor site. Furthermore, DMN-Tre labeling was reduced by treatment with TB drugs, unlike the clinically used auramine stain. [92] She has a wife and three sons.[93]. Here, we report the use of azido-modified unnatural sialic acid to identify those molecules that act as cell surface acceptors of the sialyl residue in the trans-sialidase-catalyzed reaction, which might then be involved in the immune alterations induced. Spreading of a mycobacterial cell surface lipid into host epithelial membranes promotes infectivity. View details for DOI 10.1074/jbc.M111.315473, View details for Web of Science ID 000301349400015. Using computational modeling, we designed the dendrimer scaffold and protein attachment point to resemble the native N-glycan architecture. The lipooligosaccharides (LOS) of Haemophilus ducreyi are highly sialylated, a modification that has been implicated in resistance to host defense and in virulence. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis. Breidenbach, M. A., Palaniappan, K. K., Pitcher, A. Our editors will review what youve submitted and determine whether to revise the article. The conjugation proceeds under mild conditions with excellent ligation efficiencies and in a stereoselective manner, providing glycopolymers with pendant glycans accommodated mostly in their cyclic beta-glycosidic form. Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. 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. View details for Web of Science ID 000285812000039, View details for PubMedCentralID PMC3018347. Furthermore, their dynamic behavior in synthetic membranes mirrored that of natural biomolecules. Our results suggest that both Gal-6-SO(4) and GlcNAc-6-SO(4) may contribute to L-selectin recognition, either as components of sulfosialyl-Le(X) capping groups or in internal structures. Zhu, X., Shieh, P., Su, M., Bertozzi, C. R., Zhang, W. A Bioorthogonal Reaction of N-Oxide and Boron Reagents. However, anti-HIV antibodies are found at far lower concentrations in OF compared with blood, leading to poor sensitivity and a longer period of time from infection to detection threshold. [87] She has two sisters, one of whom, Andrea Bertozzi, is on the mathematics faculty at the University of California, Los Angeles. View details for DOI 10.1021/acs.jproteome.0c00218. Schumann, B. n., Malaker, S. A., Wisnovsky, S. P., Debets, M. F., Agbay, A. J., Fernandez, D. n., Wagner, L. J., Lin, L. n., Li, Z. n., Choi, J. n., Fox, D. M., Peh, J. n., Gray, M. A., Pedram, K. n., Kohler, J. J., Mrksich, M. n., Bertozzi, C. R. An Acquired and Endogenous Glycocalyx Forms a Bidirectional "Don't Eat" and "Don't Eat Me" Barrier to Phagocytosis. We developed a baculovirus expression system for five of the seven cloned GSTs and determined their kinetic parameters using both thin-layer chromatography and a recently developed polymer dot-blot assay. A Bioorthogonal Reaction of N-Oxide and Boron Reagents. Circular dichroism of unglycosylated diptericin indicated that the peptide lacked structure both in plain buffer and in the presence of liposomes. We identified prominent localization of mucins in the pharynx of all four larval stages, in the adult hermaphrodite pharynx, vulva and anus, and in the tail of the adult male. Termed the CalFluors, these probes possess emission maxima that range from green to far red wavelengths, and enable sensitive biomolecule detection under no-wash conditions. View details for Web of Science ID 000232605600062. View details for Web of Science ID 000168932900013. Protein glycosylation can have an enormous variety of biological consequences, reflecting the molecular diversity encoded in glycan structures. Tomlin, F. M., Gerling-Driessen, U. I., Liu, Y. C., Flynn, R. A., Vangala, J. R., Lentz, C. S., Clauder-Muenster, S. n., Jakob, P. n., Mueller, W. F., Ordoez-Rueda, D. n., Paulsen, M. n., Matsui, N. n., Foley, D. n., Rafalko, A. n., Suzuki, T. n., Bogyo, M. n., Steinmetz, L. M., Radhakrishnan, S. K., Bertozzi, C. R. Ingredients for a Positive Safety Culture. Labeling cells with omega-alkynyl-palmitate does not affect membrane association of N-Ras. One of the endothelial-derived ligands for L-selectin is GlyCAM-1 (previously known as Sgp50), a mucin-like glycoprotein with sulfated, sialylated, and fucosylated O-linked oligosaccharide chains. Moreover, the ability of the Rv2131c-encoded enzyme to dephosphorylate PAP and PAPS in vivo was confirmed by functional complementation of an Escherichia coli Delta cysQ mutant. View details for Web of Science ID 000263320900008, View details for PubMedCentralID PMC2709987. Finally, we show that normal V snapping in C. glutamicum depends on complete assembly of the septal cell envelope. Hang, H. C., Yu, C., Ten Hagen, K. G., Tian, E., Winans, K. A., Tabak, L. A., Bertozzi, C. R. Probing glycosyltransferase activities with the Staudinger ligation. Kaushik, S., Barnes, J., Bainer, R. O., Sa, J. K., Woods, E. C., Kai, F., Przybyla, L., Lakins, J. N., Phillips, J. J., Nam, D., Bertozzi, C. R., Weaver, V. M. Is the Nobel Prize in Chemistry Having a Boston Red Sox Moment? Despite reports detailing a suite of sulfated glycolipids in many mycobacteria, a corresponding family of sulfotransferase genes remains uncharacterized. The advantage of this ELISA over previous assays is that a macromolecular physiological ligand is employed, rather than a fortuitous or simplified carbohydrate ligand. Bhat, R., Belardi, B., Mori, H., Kuo, P., Tam, A., Hines, W. C., Quynh-Thu Le, Q. T., Bertozzi, C. R., Bissell, M. J. Symbol Nomenclature for Graphical Representations of Glycans. View details for Web of Science ID 000226522400020, View details for Web of Science ID 000229731100007, View details for DOI 10.1002/cbic.200400148, View details for Web of Science ID 000225672400013. Cotton Medal, Texas A&M University (2020); The Gustavus John Esselen Award for Chemistry in the Public Interest, Northeast Section of the ACS (2019); Max Tishler Prize, Harvard University Dept. View details for DOI 10.1093/glycob/cwz045, View details for Web of Science ID 000493194700001. In 2015 she became a professor of chemistry at Stanford University. We report here a strategy for the synthesis of O-linked glycopeptide analogues that replaces this linkage with a thioether amenable to construction by chemoselective ligation. GlcNAc6ST-2 is a member of a family of related enzymes that act on similar carbohydrate substrates in vitro but discrete glycoproteins in vivo. Henkin, A. H., Cohen, A. S., Dubikovskaya, E. A., Park, H. M., Nikitin, G. F., Auzias, M. G., Kazantzis, M., Bertozzi, C. R., Stahl, A. Fluorogenic Azidofluoresceins for Biological Imaging. This was confirmed by enzymatic assay of the partially purified enzyme with unnatural substrates. Bertozzi is a professor Screening of the library identified an inhibitor with a K(i) value of 11 microM. View details for DOI 10.1073/pnas.2335201100, View details for Web of Science ID 000187227200045, View details for PubMedCentralID PMC299823. Macrophages continuously survey their environment in search of pathogens or apoptotic corpses or debris. However, the diversity found in glycoproteins has undermined efforts to describe the intact glycoproteome via mass spectrometry (MS). Harland, C. W., Rabuka, D., Bertozzi, C. R., Parthasarathy, R. Rv2131c from Mycobacterium tuberculosis is a CysQ 3 '-phosphoadenosine-5 '-phosphatase. 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