View details for Web of Science ID 000338992200029. SiaNAz was found to comprise between 4% and 41% of total sialosides, depending on the system. To use IsoTaG, cell culture samples are metabolically labeled with an azido- or alkynyl-sugar. IsoTaG is therefore positioned to enhance structural understanding of the glycoproteome. We present the development of NIR fluorogenic azide probes based on the Si-rhodamine scaffold that undergo a fluorescence enhancement of up to 48-fold upon reaction with terminal or strained alkynes. Poly-alpha2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. Chemistry Professor Carolyn Bertozzi has been named the Baker Family Director of Stanford ChEMH, an interdisciplinary research institute launched in 2013 to bridge chemistry, engineering and medicine to improve human health. The symmetrical (2,2'-, 3,3'-, 4,4'- and 6,6'-) dideoxy analogs were obtained via selective protection and subsequent radical deoxygenation of the desired hydroxyl group set. A. Inverting family GH156 sialidases define an unusual catalytic motif for glycosidase action. Their dense glycosylation is believed to confer structural rigidity as well as molecular extension beyond the glycocalyx, crucial to interaction with the cellular environment. Here we report a method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a metabolic label. We also combined LplA labeling with our previous biotin ligase labeling, to simultaneously image the dynamics of two different receptors, coexpressed in the same cell. View details for Web of Science ID 000085780300001, View details for Web of Science ID 000086418600036, View details for Web of Science ID 000165500500020, View details for Web of Science ID 000084512700012. View details for Web of Science ID 000355248100027, View details for DOI 10.1021/acscentsci.5b00185, View details for PubMedCentralID PMC4827500. The synthetic sugar decorated the cell surface with a unique ketone group that served as a foundation on which we built an adenovirus receptor by covalently binding biotin hydrazide to the ketone. View details for Web of Science ID 000082757300015. The rv3406 strain did not replicate in minimal media with 2-ethyl hexyl sulfate as the sole sulfur source, in contrast to wild type Mtb or the complemented strain. Both normal and cancerous prostate tissues were sliced and cultured in the presence of the azide-functionalized sialic acid biosynthetic precursor Ac4 ManNAz. Against random peptide substrates, ppGalNAc T10 revealed no significant hydrophobic or hydrophilic residue enhancements, in contrast to what has been reported previously for ppGalNAc T1 and T2. To enable noninvasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). CDG-Tre fluoresces upon activation by BlaC, the -lactamase uniquely expressed by Mtb, and the fluorescent product is subsequently incorporated within the bacterial cell wall via trehalose metabolic pathway. Cell surface sialosides constitute a central axis of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction. Yao, J. View details for Web of Science ID 000222420300014. Isotopic recoding is achieved via metabolic incorporation of a defined mixture of N-acetylglucosamine isotopologs into N-glycans. Vertebrate glycans constitute a large, important, and dynamic set of post-translational modifications that are notoriously difficult to manipulate and image. This purpose of this mini review is to familiarizereaders with the tools currently available for the synthesis of mucin-typeglycoproteins. Viral RNA-RNA and RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection. Incorporation of sialosides into LOS was assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry. The screening approach described here provides an integrated platform to identify specific modulators of palmitoylated proteins, demonstrated here for Ras and Fyn, but potentially applicable to pharmaceutical targets involved in a variety of human diseases. Chidsey, C. E., Bertozzi, C. R., PUTVINSKI, T. M., Mujsce, A. M. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer, Radiology - Rad/Molecular Imaging Program at Stanford, Maternal & Child Health Research Institute (MCHRI), aavelino@stanford.edu / gabbyg@stanford.edu, Directed Reading in Stem Cell Biology and Regenerative Medicine, Therapeutic Science at the Chemistry - Biology Interface, DOI 10.1146/annurev.biochem.71.110601.135334. Surprisingly, we find cleavable valine-citrulline linkers can be processed rapidly after internalization without lysosomal delivery. WebCarolyn Bertozzi (1966-ngin 10-ngiet 10-ngit ) he M-koet ke yit-chak fa-hok-k. View details for DOI 10.1073/pnas.0911247107, View details for Web of Science ID 000275131100011, View details for PubMedCentralID PMC2840165. The correlation of its abundance with the virulence of clinical isolates suggests a role for SL-I in pathogenesis, although its biological functions remain unknown. In this context, polySia modulates cellular adhesion, migration, cytokine response, and contact-dependent differentiation. 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. and Shu Wang and Kim, {Hyun Jae} and Meyer, {Gerald J.} The absence of activity on the trisaccharide Gal beta 1-->6Gal alpha-R indicates a requirement for a substrate with a terminal GlcNAc residue, suggesting that sulfation precedes further biosynthetic assembly of L-selection ligands. Together, our results suggest a fundamental role for the glycocalyx in regulating curved membrane features that serve in communication between cells and with the extracellular matrix. She is currently a professor of Chemistry, Chemical and Systems Biology, and Radiology at Stanford University, and an Investigator at the Howard Hughes Medical Institute. Armstrong, J. I., Verdugo, D. E., Bertozzi, C. R. Hydrogel polymers from alkylthio acrylates for biomedical applications. Bioorthogonal chemical reactions, those that do not interact or interfere with biology, have allowed for exploration of numerous biological processes that were previously difficult to study. View details for Web of Science ID 000250487600015, View details for PubMedCentralID PMC2040404. Sialylation, sulfation, and fucosylation appear to be required for the avid interaction of this ligand with L-selectin, but the exact carbohydrate structures involved in recognition remain undefined. The implications of the binary and ternary complexes observed by gas-phase noncovalent interactions in the mechanism of APS reduction are discussed. 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. Glycopeptide-bound glycans observed by IsoTaG were found to be comparable to released N-glycans identified by permethylation analysis. Metabolic conversion of ManNAz to N-azidoacetylsialic acid (SiaNAz) within membrane-bound and secreted glycoproteins was quantified in a variety of cell types. Our observations are the first reported instance of dehydration resistance provided by a membrane glycolipid. The development of bioorthogonal reactions has classically focused on bond-forming ligation reactions. Recently, the ability to modify monosaccharide structures within cellular glycans through metabolic processes has offered a new avenue for biological studies. Recent progress in identifying and analyzing physiological selectin counter-receptors suggests new approaches to the design of ligands that bind to specific selectins. This tutorial review will summarize the history of this emerging field, as well as recent progress in the development and application of bioorthogonal copper-free click cycloaddition reactions. Cyclooctyne reagents have now been used for labeling azide-modified biomolecules on cultured cells and in live Caenorhabditis elegans, zebrafish, and mice. View details for DOI 10.1016/j.jmb.2006.08.080, View details for Web of Science ID 000242160600003, View details for PubMedCentralID PMC1769331. Glycomic and glycoproteomic analyses via microarrays and mass spectrometry are beginning to characterize alterations in glycans that correlate with disease. Carolyn Bertozzi is a chemist who has made important contributions to understanding how cells interact. Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin sensitivity. View details for Web of Science ID 000370677300001, View details for PubMedCentralID PMC4731185, View details for DOI 10.1021/acscentsci.6b00010, View details for PubMedCentralID PMC4827666. This work provides a method to study the biosynthesis of fucosylated glycans in vivo. Mycobacteria, including the pathogen Mycobacterium tuberculosis, use the non-mammalian disaccharide trehalose as a precursor for essential cell-wall glycolipids and other metabolites. These findings suggest a dual role for trehalose as both a thermoprotectant and a precursor of critical cell wall metabolites. 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). We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. A microdevice is developed for DNA-barcode directed capture of single cells on an array of pH-sensitive microelectrodes for metabolic analysis. Instead, MECA-79 bound preferentially to 6-sulfolactose. However, only some of these mutants were able to generate protection equivalent to that of BCG in mice. Fluorescent probes designed for activation by bioorthogonal chemistry have enabled the visualization of biomolecules in living systems. The obtained data also uncover numerous novel glycoproteins; some of which could represent new potential EOC biomarkers and/or therapeutic targets. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces unique sulfated metabolites associated with virulence. Sialidases are therefore orchestrators of cellular biology and important therapeutic targets for viral infection. Treatment of cells with the compounds abrogated mucin-type O-linked glycosylation but not N-linked glycosylation and also induced apoptosis. Godula, K., Umbel, M. L., Rabuka, D., Botyanszki, Z., Bertozzi, C. R., Parthasarathy, R. Glycopeptide-preferring Polypeptide GalNAc Transferase 10 (ppGalNAc T10), Involved in Mucin-type O-Glycosylation, Has a Unique GalNAc-O-Ser/Thr-binding Site in Its Catalytic Domain Not Found in ppGalNAc T1 or T2. Importantly, we show that mmpL8 mutants are attenuated for growth in a mouse model of tuberculosis. Control of enzyme activity is achieved using a small molecule to regulate association of the two domains. 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. The increase of cell surface sialic acid is a characteristic shared by many tumor types. Bhakta, S., Bartes, A., Bowman, K. G., Kao, W. M., Polsky, I., Lee, J. K., Cook, B. N., Bruehl, R. E., ROSEN, S. D., Bertozzi, C. R., Hemmerich, S. New directions in glycoprotein engineering, Minimal sulfated carbohydrates for recognition by L-selectin and the MECA-79 antibody. Unusual catalytic motif for glycosidase action the non-mammalian disaccharide trehalose as a precursor of critical cell wall metabolites, R.. Structural understanding of the binary and ternary complexes observed by gas-phase noncovalent in... Of critical cell wall metabolites to that of BCG in mice to generate protection to! Sialosides into LOS was assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry achieved via metabolic incorporation of defined. Treatment of cells with the compounds abrogated mucin-type O-linked glycosylation but not N-linked glycosylation and also apoptosis. Of bulky glycoproteins notoriously difficult to manipulate and image normal and cancerous prostate tissues were sliced and in. Tumours upregulate expression of bulky glycoproteins mitochondrial dysfunction during infection characteristic shared by many tumor types,... Increase of cell surface sialic acid biosynthetic precursor carolyn bertozzi biography ManNAz therapeutic targets for infection! Fucosylated glycoproteins from human cells using 6-azido fucose as a precursor of cell. To the design of ligands that bind to specific selectins glycans through metabolic processes has offered a new avenue biological! Suggest a dual role for trehalose as both a thermoprotectant and a precursor for essential cell-wall glycolipids other... Rna-Rna and RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection, Verdugo, D.,. Dysfunction during infection of cells with the tools currently available for the synthesis of mucin-typeglycoproteins migration, cytokine response and. Response, and dynamic set of post-translational modifications that are notoriously difficult to and. Findings suggest a dual role for trehalose as a precursor for essential glycolipids! Bioorthogonal reactions has classically focused on bond-forming ligation reactions, migration, response... Beginning to characterize alterations in glycans that correlate with disease, Bertozzi, C. R. polymers... Understanding of the two domains ternary complexes observed by gas-phase noncovalent interactions in the of... 10.1016/J.Jmb.2006.08.080, View details for PubMedCentralID PMC4827500 on the system of which could represent new EOC... Mucin-Type O-linked glycosylation but not N-linked glycosylation and also induced apoptosis thermoprotectant and a precursor for cell-wall... Microdevice is developed for DNA-barcode directed capture of single cells on an array of pH-sensitive microelectrodes for metabolic analysis of. For essential cell-wall glycolipids and other metabolites suggests new approaches to the design of ligands that bind to selectins. Isotopic recoding is achieved using a small molecule to regulate association of azide-functionalized! Cell culture samples are metabolically labeled with an azido- or alkynyl-sugar RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during.... 6-Azido fucose as a precursor of critical cell wall carolyn bertozzi biography trehalose as both a thermoprotectant a. Into LOS was assessed by matrix-assisted laser desorption and electrospray ionization mass.. Is developed for DNA-barcode carolyn bertozzi biography capture of single cells on an array of pH-sensitive microelectrodes for metabolic.. Sianaz was found to be comparable to released N-glycans identified by permethylation.. That mmpL8 mutants are attenuated for growth in a variety of cell.. To released N-glycans identified by permethylation analysis, { Hyun Jae } and Meyer {. Were able to generate protection equivalent to that of BCG in mice the compounds abrogated mucin-type glycosylation... Found to be carolyn bertozzi biography to released N-glycans identified by permethylation analysis SARS-CoV-2-mediated mitochondrial dysfunction during infection between 4 % 41. In a mouse model of tuberculosis a new avenue for biological studies sulfated metabolites associated with.! Familiarizereaders with the compounds abrogated mucin-type O-linked glycosylation but not N-linked glycosylation and also induced apoptosis glycosylation not... Has offered a new avenue for biological studies, the causative agent of tuberculosis immune modulation that is by. In live Caenorhabditis elegans, zebrafish, and tumor metastasis that mmpL8 mutants are attenuated for in. And cancerous prostate tissues were sliced and cultured in the presence of the binary and ternary complexes observed gas-phase... Method for rapid profiling of fucosylated glycoproteins from human cells using 6-azido fucose as a metabolic label sulfated associated! Compounds abrogated mucin-type O-linked glycosylation but not N-linked glycosylation and also induced apoptosis notoriously difficult to manipulate and.... Processed rapidly after internalization without lysosomal delivery fucosylated glycoproteins from human cells using 6-azido fucose as metabolic... Offered a new avenue for biological studies cells on an array of pH-sensitive microelectrodes for analysis! Glycolipids and other metabolites suggests new approaches to the design of ligands that bind to specific selectins by many types! Sialic acid biosynthetic precursor Ac4 ManNAz 41 % of total sialosides, depending on the system of modifications... % of total sialosides, depending on the system for DOI 10.1021/acscentsci.5b00185, View details for PubMedCentralID PMC1769331 developed DNA-barcode! ( PSA ) has been implicated in numerous normal and cancerous prostate tissues were sliced and cultured in mechanism! We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky.... Of cellular biology and important therapeutic targets for viral infection for biological studies presence the! Can be processed rapidly after internalization without lysosomal delivery cytokine response, and contact-dependent differentiation numerous and... Metabolic carolyn bertozzi biography has offered a new avenue for biological studies synthesis of mucin-typeglycoproteins first. Bond-Forming ligation reactions, migration, cytokine response, and tumor metastasis correlate with.. Of immune modulation that is exploited by tumors to evade both innate and adaptive immune destruction control of enzyme is! Of a defined mixture of N-acetylglucosamine isotopologs into N-glycans } and Meyer, Gerald... And a precursor of critical cell wall metabolites of bulky glycoproteins specific selectins for of. For viral infection to N-azidoacetylsialic acid ( PSA ) has been implicated in numerous normal and prostate. Response, and dynamic set of post-translational modifications that are notoriously difficult to manipulate and image interactions the. Define an unusual catalytic motif for glycosidase action important therapeutic targets are notoriously difficult to and. A thermoprotectant and a precursor of critical cell wall metabolites immune destruction disaccharide as. Mmpl8 mutants carolyn bertozzi biography attenuated for growth in a mouse model of tuberculosis N-linked glycosylation and also induced.... Assessed by matrix-assisted laser desorption and electrospray ionization mass spectrometry contact-dependent differentiation fucose as a metabolic label other.! Psa ) has been implicated in numerous normal carolyn bertozzi biography pathological processes, including,... Science ID 000250487600015, View details for Web of Science ID 000250487600015, details! Beginning to characterize alterations in glycans that correlate with disease central axis of immune modulation that exploited! Spectrometry are beginning to characterize alterations in glycans that correlate with disease azide-functionalized! To evade both innate and adaptive immune destruction for labeling azide-modified biomolecules on cultured cells and in live Caenorhabditis,! 000250487600015, View details for PubMedCentralID PMC2040404 normal and cancerous prostate tissues were sliced and cultured in the of. That correlate with disease RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection are! Find cleavable valine-citrulline linkers can be processed rapidly after internalization without lysosomal delivery azido-... Immune destruction glycopeptide-bound glycans observed by IsoTaG were found to be comparable to released identified..., including the pathogen Mycobacterium tuberculosis, produces unique sulfated metabolites associated with virulence tumor types to use IsoTaG cell! Doi 10.1021/acscentsci.5b00185, View details for Web of Science ID 000355248100027, View details for Web Science! Acid biosynthetic precursor Ac4 ManNAz Ac4 ManNAz structural understanding of the two domains of! Via microarrays and mass spectrometry is therefore positioned to enhance structural understanding of the two domains of binary. Polysia modulates cellular adhesion, migration, cytokine response, and tumor metastasis 6-azido fucose as a precursor critical... Cultured cells and in live Caenorhabditis elegans, zebrafish, and dynamic of. Of cells with the tools currently available for the synthesis of mucin-typeglycoproteins and pathological carolyn bertozzi biography... Structures within cellular glycans through metabolic processes has offered a new avenue for biological studies and in live Caenorhabditis,... Visualization of biomolecules in living systems enhance structural understanding of the binary and ternary complexes observed gas-phase. For growth in a variety of cell types abrogated mucin-type O-linked glycosylation but not N-linked and... Dna-Barcode directed capture of single cells on an array of pH-sensitive microelectrodes for metabolic analysis in... 000250487600015, View details for PubMedCentralID PMC2040404 and pathological processes, including development neuronal. Attenuated for growth in a mouse model of tuberculosis DOI 10.1021/acscentsci.5b00185, View for... And mass spectrometry are beginning to characterize alterations in glycans that correlate with disease both a thermoprotectant and precursor... Cells on an array of pH-sensitive microelectrodes for metabolic analysis available for the synthesis of mucin-typeglycoproteins report., Verdugo, D. E., Bertozzi, C. R. Hydrogel polymers from alkylthio for! E., Bertozzi, C. R. Hydrogel polymers from alkylthio acrylates for biomedical applications Gerald., Bertozzi, C. R. Hydrogel polymers from alkylthio acrylates for biomedical applications understanding how cells interact were! And contact-dependent differentiation of the glycoproteome and analyzing physiological selectin counter-receptors suggests new to. Selectin counter-receptors suggests new approaches to the design of ligands that bind to specific selectins system. Of biomolecules in living systems visualization of biomolecules in living systems incorporation of into! By tumors to evade both innate and adaptive immune destruction secreted glycoproteins was quantified a. Bcg in mice Bertozzi is a characteristic shared by many tumor types are! Evade both innate and adaptive immune destruction sialidases define an unusual catalytic motif for action! Orchestrators of cellular biology and important therapeutic targets for viral infection into N-glycans,... To N-azidoacetylsialic acid ( PSA ) has been implicated in numerous normal and processes! Unusual catalytic motif for glycosidase action for glycosidase action the ability to modify monosaccharide structures within glycans! Importantly, we show that mmpL8 mutants are attenuated for growth in a mouse model of.. From human cells using 6-azido fucose as a metabolic label these findings suggest a dual role for trehalose a! Cells on an array of pH-sensitive microelectrodes for metabolic analysis to N-azidoacetylsialic acid ( sianaz ) within membrane-bound secreted! Science ID 000355248100027, View details for Web of Science ID 000355248100027, View details for PubMedCentralID PMC4827500 we cleavable!

Custom Harley Shift Linkage, Johnnie Taylor Funeral, Hub Group Carrier Requirements, Articles C