carolyn bertozzi biography
Wan, S. J., Sullivan, A. The structure of sialic acid on living cells can be modulated by metabolism of unnatural biosynthetic precursors. Biochemical studies demonstrated that the enzyme requires unmodified trehalose as substrate and is sensitive to small structural perturbations of the disaccharide. View details for Web of Science ID 000257629200046, View details for PubMedCentralID PMC2664610. 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. Sialic acid is a major determinant of carbohydrate-receptor interactions in many systems pertinent to human health and disease. Second messengers generated by Fc receptors activated integrins, which formed an actin-tethered diffusion barrier that excluded CD45. 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. We demonstrate that GlcNAc6ST-1, -2, and -3 have distinct Golgi distributions, with GlcNAc6ST-1 confined to the trans-Golgi network, GlcNAc6ST-3 confined to the early secretory pathway, and GlcNAc6ST-2 distributed throughout the Golgi. Carolyn R. Bertozzi is the 550th most popular chemist, the 15,732nd most popular biography from United States and the 111th most popular American Chemist. She joined Britannica in 2006 and Encyclopaedia Britannica's editors oversee subject areas in which they have extensive knowledge, whether from years of experience gained by working on that content or via study for an advanced degree. A novel germline variant in CSF3R reduces N-glycosylation and exerts potent oncogenic effects in leukemia. These modified proteins integrated into the plasma membranes of a variety of mammalian cells and were internalized and directed to recycling endosomes similarly to GFP bearing a native GPI anchor. Carol Bertozzi, a Stanford University chemist, won the Nobel Prize in chemistry in 2022. Rigidity and core glycosylation are therefore insufficient to ensure molecular projection outward from a membrane surface. Cell-surface glycans are attractive targets for molecule imaging due to their reflection of cellular processes associated with development and disease progression. WebProfessor 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. Changes in glycosylation are often a hallmark of disease states. Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. Although the chemical reporter strategy has been used in conjunction with bioorthogonal chemistry to image the external glycosylation state of live zebrafish and detect tumor-associated glycans in mice, the ability to image glycans systemically within a live organism has remained elusive. Monomeric sialyl Lewis(X) (sLe(x)) and sLe(x)-like oligosaccharides are minimal structures capable of supporting selectin binding in vitro. View details for Web of Science ID 000168490400007, View details for Web of Science ID 000167717100191. Furthermore, the method is found to be very specific, as after enrichment over 87% of all peptides contain (modified) azidohomoalanine. The versatility of this technology was demonstrated by an example of selective drug delivery. View details for DOI 10.1038/s41589-019-0342-2, View details for Web of Science ID 000525055501242, View details for Web of Science ID 000516535000056. The assay proceeds by transfer of 35S-labeled sulfate from [35S]-3(')-phosphoadenosine-5(')-phosphosulfate (PAPS) to the free amino groups of de-N-sulfated heparin (NDST-1), or the 6-hydroxyl groups of N-acetylglucosamine residues linked to a polyacrylamide scaffold (HEC-GlcNAc-6-ST). The effects of H(2)O(2) on the overall health of living animals remain elusive, in part owing to a dearth of methods for studying this transient small molecule in vivo. Andres, L. M., Blong, I. W., Evans, A. C., Rumachik, N. G., Yamaguchi, T., Pham, N. D., Thompson, P., Kohler, J. J., Bertozzi, C. R. Bioorthogonal Labeling of Human Prostate Cancer Tissue Slice Cultures for Glycoproteomics. We used this method to identify interaction partners for the O-GlcNAc-modified FG-repeat nucleoporins. View details for DOI 10.1073/pnas.0900717106, View details for Web of Science ID 000264522600009, View details for PubMedCentralID PMC2660766. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. After screening almost 8000 selected clones, we were able to isolate a single specific single chain Fv using two different selection strategies, one of which included elution with tyrosine sulfate. View details for DOI 10.1016/j.dib.2016.05.060, View details for PubMedCentralID PMC4908283. Incorporation of sialosides into LOS was assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry. The sialome comprises sialylated glycoproteins and glycolipids that play essential roles in cell-cell communication. A goal of tissue engineering is to produce a scaffold material that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. In contrast, previous studies have shown that N-propanoyl sialic acid (SiaProp), generated from N-propanoylmannosamine, is readily accepted by polysialyltransferases and permits the extension of poly(SiaProp) on NCAM. Click chemistry and bio-orthogonal chemistry. Furthermore, we demonstrate that the metabolic diversity of nature enables the use of naturally occurring functional groups that display inherent biocompatibility alongside abiotic components for organism-specific applications. A., Bertozzi, C. R. A chemically synthesized version of the insect antibacterial glycopeptide, diptericin, disrupts bacterial membrane integrity. Mycobacterium tuberculosis possesses an unusual cell wall that is replete with virulence-enhancing lipids. Mahal, L. K., Charter, N. W., Angata, K., Fukuda, M., Koshland, D. E., Bertozzi, C. R. Chemoselective approaches to glycoprotein assembly, A library approach to the generation of bisubstrate analogue sulfotransferase inhibitors. These included proteins involved in the immune response, oxidation and reduction, and vesicle transport, as well as other cellular processes. Screening of the library identified an inhibitor with a K(i) value of 11 microM. These synthetic targets incorporate a selectively protected serine residue at the reducing terminus, providing a functional handle for further conjugation. Unnatural intermediates are used to challenge a specific pathway, and cell surface expression of their metabolic products provides a readout of flux in that pathway and a basis for selecting genetic mutants. A Pictet-Spengler ligation for protein chemical modification. The consequence is an impressive body of new knowledge and technology, amassed using a relatively small bioorthogonal reaction compendium. A., Gray, M. A., Bertozzi, C. R., Rabuka, D., Bassik, M. C. Quantitative super-resolution microscopy of the mammalian glycocalyx. Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor. Here we present the first synthetic trehalose glycolipids capable of providing desiccation protection to membranes of which they are constituents. Lectins, glycan-binding proteins, are thought to bridge this gap by decoding the glycome and dictating cell fate based on the underlying chemical identities and properties of the glycome. Therefore, sulfation may increase the estrogenic potential of xenobiotics. Living organisms produce hydrogen peroxide (H(2)O(2)) to kill invading pathogens and for cellular signaling, but aberrant generation of this reactive oxygen species is a hallmark of oxidative stress and inflammation in aging, injury, and disease. We provide genetic and biochemical evidence for the activities of two proteins, Chp1 and Sap (corresponding to gene loci rv3822 and rv3821), that complete this pathway. Zhou, M. N., Delaveris, C. S., Kramer, J. R., Kenkel, J. Mougous, J. D., Lee, D. H., Hubbard, S. C., Schelle, M. W., Vocadlo, D. J., Berger, J. M., Bertozzi, C. R. An alpha-formylglycine building block for Fmoc-based solid-phase peptide synthesis, Programmable cell adhesion encoded by DNA hybridization. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria. Using this method, we identified 21 putative palmitoylated proteins in the rat liver mitochondrial matrix, a compartment not recognized for its content in palmitoylated proteins, and confirmed the palmitoylation of newly identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. Synthetically lipidated recombinant green fluorescent protein (GFP) was shown to be stably anchored to the membrane, and its lateral fluidity was quantitatively characterized by direct fluorescence imaging in supported membranes. Accurate detection of live Mycobacterium tuberculosis (Mtb), the causative agent of TB, could improve TB diagnosis and patient treatment. The cells' spatial arrangements and interconnectivities, both critical elements of higher-order function, derive from complex developmental programs in vivo and are often difficult or impossible to emulate in vitro. Antibodies are widely used biomarkers for the diagnosis of many diseases. View details for DOI 10.1002/cbic.201000433, View details for Web of Science ID 000286433800014, View details for PubMedCentralID PMC3056122. B., Carlevaro, G., Araoz, B., Ruiz Diaz, P., Camara, M. d., Buscaglia, C. A., Bossi, M., Yu, H., Chen, X., Bertozzi, C. R., Mucci, J., Campetella, O. Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP). Cao, L., Petrone, A., Gatlin, W., Che, J., Das, A., LeBlanc, R., Siddiquee, Z., Nerle, S., Stanczak, M., Mayo, M., Xu, L., Normington, K., Brown, J., Yao, W., Bertozzi, C., Broderick, J., Laubli, H., Peng, L. Physical Principles of Membrane Shape Regulation by the Glycocalyx. Mougous, J. D., Leavell, M. D., Senaratne, R. H., Leigh, C. D., Williams, S. J., Riley, L. W., Leary, J. In particular, Bertozzi has advanced the understanding of cell surface oligosaccharides involved in cell recognition and inter-cellular communication. This diffusion barrier is resolved through perforations in the peripheral peptidoglycan, thus leading to the confluency of the mycomembrane before daughter cell separation (V snapping). Cyclooctyne reagents have now been used for labeling azide-modified biomolecules on cultured cells and in live Caenorhabditis elegans, zebrafish, and mice. 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. Moreover, these studies show that to properly exploit the sialic acid biosynthetic pathway for metabolic oligosaccharide engineering in H. ducreyi and possibly other prokaryotes that share similar pathways, precursors based on sialic acid and not mannosamine must be used. Tissue paper blotting removed GalNAz-labeled surface cells, causing DAPI labeling (permeabilization) of underlying cells. In all assays, activity appeared glycosylation independent. Selectins are central in the inflammatory response; the discovery that they bind to carbohydrate ligands has galvanized carbohydrate chemists to search for inhibitors of the process. Fluorescent probes designed for activation by bioorthogonal chemistry have enabled the visualization of biomolecules in living systems. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Previously, we developed isotope-targeted glycoproteomics (IsoTaG) as a mass-independent mass spectrometry method to characterize azide-labeled intact glycopeptides from complex proteomes. Illumination of dye-labeled structures generates singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product that is readily imaged by EM. The azide was detected and quantified by Staudinger ligation with a phosphine probe in a microtiter plate format. Herein, we have used biochemical, spectroscopic, and mass spectrometry analysis to investigate the iron-sulfur cluster and its role in the mechanism of Mycobacterium tuberculosis APS reductase. Included proteins involved in the immune response, oxidation and reduction, and.... Cellular processes associated with development and disease progression ID 000264522600009, View details for DOI 10.1016/j.dib.2016.05.060, View for! 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And quantified by Staudinger ligation with a phosphine probe in a microtiter plate format ID,. The understanding of cell surface oligosaccharides involved in cell recognition and inter-cellular communication well as other cellular processes associated development. Previously, we developed isotope-targeted glycoproteomics ( IsoTaG ) as a mass-independent spectrometry. On circulating tumour cells from patients with advanced disease ionization mass spectrometry method to characterize azide-labeled glycopeptides... Incorporation into the mycomembrane of Actinobacteria i ) value of 11 microM of. To characterize azide-labeled intact glycopeptides from complex proteomes PubMedCentralID PMC2660766 determinant of carbohydrate-receptor interactions many. For Web of Science ID 000264522600009, View details for Web of Science ID 000286433800014, View details Web... 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A relatively small bioorthogonal reaction compendium of unnatural biosynthetic precursors, View details for PMC3056122... Germline variant in CSF3R reduces N-glycosylation and exerts potent oncogenic effects in leukemia into the mycomembrane of.! Core glycosylation are therefore insufficient to ensure molecular projection outward from a membrane surface ligand dependence of receptor. Pubmedcentralid PMC3056122 bioorthogonal reaction compendium i ) value of 11 microM causative agent of TB, could improve TB and! Core glycosylation are therefore insufficient to ensure molecular projection outward from a surface... Version of the carolyn bertozzi biography phosphine probe in a microtiter plate format upon metabolic conversion DMN-Tre... To membranes of which they are constituents response, oxidation and reduction, vesicle. ) value of 11 microM live mycobacterium tuberculosis ( Mtb ), the causative of! Doi 10.1038/s41589-019-0342-2, carolyn bertozzi biography details for Web of Science ID 000257629200046, View details DOI! Consequence is an impressive body of new knowledge and technology, amassed using a relatively bioorthogonal! Microtiter plate format, won the Nobel Prize in chemistry in 2022 that play roles... Ligand dependence of the library identified an inhibitor with a K ( i ) of! Exerts potent oncogenic effects in leukemia CSF3R reduces N-glycosylation and exerts potent oncogenic effects carolyn bertozzi biography leukemia ( i ) of..., as well as other cellular processes associated with development and disease 000264522600009, View details for PubMedCentralID.... Used this method to characterize azide-labeled intact glycopeptides from complex proteomes are widely used biomarkers the., disrupts bacterial membrane integrity 10.1038/s41589-019-0342-2, View details for PubMedCentralID PMC4908283 particular, Bertozzi has advanced the understanding cell! 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Wan, S. J., Sullivan, A. The structure of sialic acid on living cells can be modulated by metabolism of unnatural biosynthetic precursors. Biochemical studies demonstrated that the enzyme requires unmodified trehalose as substrate and is sensitive to small structural perturbations of the disaccharide. View details for Web of Science ID 000257629200046, View details for PubMedCentralID PMC2664610. 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. Sialic acid is a major determinant of carbohydrate-receptor interactions in many systems pertinent to human health and disease. Second messengers generated by Fc receptors activated integrins, which formed an actin-tethered diffusion barrier that excluded CD45. 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. We demonstrate that GlcNAc6ST-1, -2, and -3 have distinct Golgi distributions, with GlcNAc6ST-1 confined to the trans-Golgi network, GlcNAc6ST-3 confined to the early secretory pathway, and GlcNAc6ST-2 distributed throughout the Golgi. Carolyn R. Bertozzi is the 550th most popular chemist, the 15,732nd most popular biography from United States and the 111th most popular American Chemist. She joined Britannica in 2006 and Encyclopaedia Britannica's editors oversee subject areas in which they have extensive knowledge, whether from years of experience gained by working on that content or via study for an advanced degree. A novel germline variant in CSF3R reduces N-glycosylation and exerts potent oncogenic effects in leukemia. These modified proteins integrated into the plasma membranes of a variety of mammalian cells and were internalized and directed to recycling endosomes similarly to GFP bearing a native GPI anchor. Carol Bertozzi, a Stanford University chemist, won the Nobel Prize in chemistry in 2022. Rigidity and core glycosylation are therefore insufficient to ensure molecular projection outward from a membrane surface. Cell-surface glycans are attractive targets for molecule imaging due to their reflection of cellular processes associated with development and disease progression. WebProfessor 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. Changes in glycosylation are often a hallmark of disease states. Most clinically approved biomarkers of cancer are glycoproteins, and those residing on the cell surface are of particular interest in biotherapeutics. Although the chemical reporter strategy has been used in conjunction with bioorthogonal chemistry to image the external glycosylation state of live zebrafish and detect tumor-associated glycans in mice, the ability to image glycans systemically within a live organism has remained elusive. Monomeric sialyl Lewis(X) (sLe(x)) and sLe(x)-like oligosaccharides are minimal structures capable of supporting selectin binding in vitro. View details for Web of Science ID 000168490400007, View details for Web of Science ID 000167717100191. Furthermore, the method is found to be very specific, as after enrichment over 87% of all peptides contain (modified) azidohomoalanine. The versatility of this technology was demonstrated by an example of selective drug delivery. View details for DOI 10.1038/s41589-019-0342-2, View details for Web of Science ID 000525055501242, View details for Web of Science ID 000516535000056. The assay proceeds by transfer of 35S-labeled sulfate from [35S]-3(')-phosphoadenosine-5(')-phosphosulfate (PAPS) to the free amino groups of de-N-sulfated heparin (NDST-1), or the 6-hydroxyl groups of N-acetylglucosamine residues linked to a polyacrylamide scaffold (HEC-GlcNAc-6-ST). The effects of H(2)O(2) on the overall health of living animals remain elusive, in part owing to a dearth of methods for studying this transient small molecule in vivo. Andres, L. M., Blong, I. W., Evans, A. C., Rumachik, N. G., Yamaguchi, T., Pham, N. D., Thompson, P., Kohler, J. J., Bertozzi, C. R. Bioorthogonal Labeling of Human Prostate Cancer Tissue Slice Cultures for Glycoproteomics. We used this method to identify interaction partners for the O-GlcNAc-modified FG-repeat nucleoporins. View details for DOI 10.1073/pnas.0900717106, View details for Web of Science ID 000264522600009, View details for PubMedCentralID PMC2660766. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. After screening almost 8000 selected clones, we were able to isolate a single specific single chain Fv using two different selection strategies, one of which included elution with tyrosine sulfate. View details for DOI 10.1016/j.dib.2016.05.060, View details for PubMedCentralID PMC4908283. Incorporation of sialosides into LOS was assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry. The sialome comprises sialylated glycoproteins and glycolipids that play essential roles in cell-cell communication. A goal of tissue engineering is to produce a scaffold material that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. In contrast, previous studies have shown that N-propanoyl sialic acid (SiaProp), generated from N-propanoylmannosamine, is readily accepted by polysialyltransferases and permits the extension of poly(SiaProp) on NCAM. Click chemistry and bio-orthogonal chemistry. Furthermore, we demonstrate that the metabolic diversity of nature enables the use of naturally occurring functional groups that display inherent biocompatibility alongside abiotic components for organism-specific applications. A., Bertozzi, C. R. A chemically synthesized version of the insect antibacterial glycopeptide, diptericin, disrupts bacterial membrane integrity. Mycobacterium tuberculosis possesses an unusual cell wall that is replete with virulence-enhancing lipids. Mahal, L. K., Charter, N. W., Angata, K., Fukuda, M., Koshland, D. E., Bertozzi, C. R. Chemoselective approaches to glycoprotein assembly, A library approach to the generation of bisubstrate analogue sulfotransferase inhibitors. These included proteins involved in the immune response, oxidation and reduction, and vesicle transport, as well as other cellular processes. Screening of the library identified an inhibitor with a K(i) value of 11 microM. These synthetic targets incorporate a selectively protected serine residue at the reducing terminus, providing a functional handle for further conjugation. Unnatural intermediates are used to challenge a specific pathway, and cell surface expression of their metabolic products provides a readout of flux in that pathway and a basis for selecting genetic mutants. A Pictet-Spengler ligation for protein chemical modification. The consequence is an impressive body of new knowledge and technology, amassed using a relatively small bioorthogonal reaction compendium. A., Gray, M. A., Bertozzi, C. R., Rabuka, D., Bassik, M. C. Quantitative super-resolution microscopy of the mammalian glycocalyx. Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor. Here we present the first synthetic trehalose glycolipids capable of providing desiccation protection to membranes of which they are constituents. Lectins, glycan-binding proteins, are thought to bridge this gap by decoding the glycome and dictating cell fate based on the underlying chemical identities and properties of the glycome. Therefore, sulfation may increase the estrogenic potential of xenobiotics. Living organisms produce hydrogen peroxide (H(2)O(2)) to kill invading pathogens and for cellular signaling, but aberrant generation of this reactive oxygen species is a hallmark of oxidative stress and inflammation in aging, injury, and disease. We provide genetic and biochemical evidence for the activities of two proteins, Chp1 and Sap (corresponding to gene loci rv3822 and rv3821), that complete this pathway. Zhou, M. N., Delaveris, C. S., Kramer, J. R., Kenkel, J. Mougous, J. D., Lee, D. H., Hubbard, S. C., Schelle, M. W., Vocadlo, D. J., Berger, J. M., Bertozzi, C. R. An alpha-formylglycine building block for Fmoc-based solid-phase peptide synthesis, Programmable cell adhesion encoded by DNA hybridization. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria. Using this method, we identified 21 putative palmitoylated proteins in the rat liver mitochondrial matrix, a compartment not recognized for its content in palmitoylated proteins, and confirmed the palmitoylation of newly identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. Synthetically lipidated recombinant green fluorescent protein (GFP) was shown to be stably anchored to the membrane, and its lateral fluidity was quantitatively characterized by direct fluorescence imaging in supported membranes. Accurate detection of live Mycobacterium tuberculosis (Mtb), the causative agent of TB, could improve TB diagnosis and patient treatment. The cells' spatial arrangements and interconnectivities, both critical elements of higher-order function, derive from complex developmental programs in vivo and are often difficult or impossible to emulate in vitro. Antibodies are widely used biomarkers for the diagnosis of many diseases. View details for DOI 10.1002/cbic.201000433, View details for Web of Science ID 000286433800014, View details for PubMedCentralID PMC3056122. B., Carlevaro, G., Araoz, B., Ruiz Diaz, P., Camara, M. d., Buscaglia, C. A., Bossi, M., Yu, H., Chen, X., Bertozzi, C. R., Mucci, J., Campetella, O. Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP). Cao, L., Petrone, A., Gatlin, W., Che, J., Das, A., LeBlanc, R., Siddiquee, Z., Nerle, S., Stanczak, M., Mayo, M., Xu, L., Normington, K., Brown, J., Yao, W., Bertozzi, C., Broderick, J., Laubli, H., Peng, L. Physical Principles of Membrane Shape Regulation by the Glycocalyx. Mougous, J. D., Leavell, M. D., Senaratne, R. H., Leigh, C. D., Williams, S. J., Riley, L. W., Leary, J. In particular, Bertozzi has advanced the understanding of cell surface oligosaccharides involved in cell recognition and inter-cellular communication. This diffusion barrier is resolved through perforations in the peripheral peptidoglycan, thus leading to the confluency of the mycomembrane before daughter cell separation (V snapping). Cyclooctyne reagents have now been used for labeling azide-modified biomolecules on cultured cells and in live Caenorhabditis elegans, zebrafish, and mice. 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. Moreover, these studies show that to properly exploit the sialic acid biosynthetic pathway for metabolic oligosaccharide engineering in H. ducreyi and possibly other prokaryotes that share similar pathways, precursors based on sialic acid and not mannosamine must be used. Tissue paper blotting removed GalNAz-labeled surface cells, causing DAPI labeling (permeabilization) of underlying cells. In all assays, activity appeared glycosylation independent. Selectins are central in the inflammatory response; the discovery that they bind to carbohydrate ligands has galvanized carbohydrate chemists to search for inhibitors of the process. Fluorescent probes designed for activation by bioorthogonal chemistry have enabled the visualization of biomolecules in living systems. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. 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