Sialic acids are nine-carbon-backbone sugars that occupy outermost positions on vertebrate cells ... more Sialic acids are nine-carbon-backbone sugars that occupy outermost positions on vertebrate cells and secreted sialoglycoproteins. These negatively charged hydrophilic carbohydrates have a variety of biological, biophysical and immunological functions. Mucosal surfaces and secretions of the mouth, airway, gut and vagina are especially sialoglycan-rich. Given their prominent positions and important functions, a variety of microbial strategies have targeted host sialic acids for adherence, mimicry and/or degradation. Here we review the roles of bacterial sialidases (neuraminidases) during colonization and pathogenesis of mammalian mucosal surfaces. Evidence is presented to support the myriad roles of mucosal sialoglycans in protecting the host from bacterial infection. In opposition, many bacteria hydrolyse sialic acids during associations with the gastrointestinal, oral, respiratory and reproductive tracts. Sialidases promote bacterial survival in mucosal niche environments in several...
Global advances in health and medicine : improving healthcare outcomes worldwide, 2013
The urinary tract is a common site of infection in humans. During pregnancy, urinary tract infect... more The urinary tract is a common site of infection in humans. During pregnancy, urinary tract infection (UTI) is associated with increased risks of maternal and neonatal morbidity and mortality, even when the infection is asymptomatic. By mapping available rates of UTI in pregnancy across different populations, we emphasize this as a problem of global significance. Many countries with high rates of preterm birth and neonatal mortality also have rates of UTI in pregnancy that exceed rates seen in more developed countries. A global analysis of the etiologies of UTI revealed familiar culprits as well as emerging threats. Screening and treatment of UTI have improved birth outcomes in several more developed countries and would likely improve maternal and neonatal health worldwide. However, challenges of implementation in resource-poor settings must be overcome. We review the nature of the barriers occurring at each step of the screening and treatment pipeline and highlight steps necessary t...
Covalent bond formation to proteins is made difficult by their multiple unprotected functional gr... more Covalent bond formation to proteins is made difficult by their multiple unprotected functional groups and normally low concentrations. A water-soluble sulfonated bathophenanthroline ligand (2) was used to promote a highly efficient Cu(I)-mediated azide-alkyne cycloaddition (CuAAC) reaction for the chemoselective attachment of biologically relevant molecules to cowpea mosaic virus (CPMV). The ligated substrates included complex sugars, peptides, poly(ethylene oxide) polymers, and the iron carrier protein transferrin, with routine success even for cases that were previously resistant to azide-alkyne coupling using the conventional ligand tris(triazolyl)amine (1). The use of 4-6 equiv of substrate was sufficient to achieve loadings of 60-115 molecules/virion in yields of 60-85%. Although it is sensitive to oxygen, the reliably efficient performance of the Cu.2 system makes it a useful tool for demanding bioconjugation applications.
Journal of the American Chemical Society, Jan 4, 2004
Copper-based catalysts for the 1,3-dipolar cycloaddition of azides and alkynes were screened in p... more Copper-based catalysts for the 1,3-dipolar cycloaddition of azides and alkynes were screened in parallel fashion using a fluorescence quenching assay. The method was designed to identify systems able to accelerate the coupling of reactants at micromolar concentrations in aqueous mixtures and to obtain quantitative comparisons of their activities. In addition to the tris(triazolylamines) previously reported, two types of compounds (bipy/phen and 2-pyridyl Schiff bases) were found to exhibit significant ligand-accelerated catalysis, with one complex showing especially dramatic rate enhancements. Preliminary explorations of the dependence of reaction rate on pH, ligand:Cu ratio, and Cu concentration are described.
Virtually all cells in the body have an intracellular clockwork based on a negative feedback mech... more Virtually all cells in the body have an intracellular clockwork based on a negative feedback mechanism. The circadian timekeeping system in mammals is a hierarchical multi-oscillator network, with the suprachiasmatic nuclei (SCN) acting as the central pacemaker. The SCN synchronizes to daily light-dark cycles and coordinates rhythmic physiology and behavior. Synchronization in the SCN and at the organismal level is a key feature of the circadian clock system. In particular, intercellular coupling in the SCN synchronizes neuron oscillators and confers robustness against perturbations. Recent advances in our knowledge of and ability to manipulate circadian rhythms make available cell-based clock models, which lack strong coupling and are ideal for target discovery and chemical biology.
Desorption/ionization on silicon mass spectrometry (DIOS-MS) is a matrix-less laser vaporization ... more Desorption/ionization on silicon mass spectrometry (DIOS-MS) is a matrix-less laser vaporization method for generating gas-phase ions. The physical properties of the silicon surfaces are crucial to DIOS-MS performance and are controlled by the selection of silicon type and the silicon etching conditions. DIOS-MS has been examined for its applicability to small-molecule analysis, quantitative studies, reaction monitoring, chromatography, protein identification, and
... David D. Dıaz, Warren G. Lewis, and MG Finnà Department of Chemistry and The Skaggs Institute... more ... David D. Dıaz, Warren G. Lewis, and MG Finnà Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute ... Bull., 49, 933 (2001); A. Donetti, E. Cereda, E. Bellora, A. Gallazzi, C. Bazzano, P. Vanoni, P. Del Soldato, R. Micheletti, F ...
Sialic acids are nine-carbon-backbone sugars that occupy outermost positions on vertebrate cells ... more Sialic acids are nine-carbon-backbone sugars that occupy outermost positions on vertebrate cells and secreted sialoglycoproteins. These negatively charged hydrophilic carbohydrates have a variety of biological, biophysical and immunological functions. Mucosal surfaces and secretions of the mouth, airway, gut and vagina are especially sialoglycan-rich. Given their prominent positions and important functions, a variety of microbial strategies have targeted host sialic acids for adherence, mimicry and/or degradation. Here we review the roles of bacterial sialidases (neuraminidases) during colonization and pathogenesis of mammalian mucosal surfaces. Evidence is presented to support the myriad roles of mucosal sialoglycans in protecting the host from bacterial infection. In opposition, many bacteria hydrolyse sialic acids during associations with the gastrointestinal, oral, respiratory and reproductive tracts. Sialidases promote bacterial survival in mucosal niche environments in several...
Global advances in health and medicine : improving healthcare outcomes worldwide, 2013
The urinary tract is a common site of infection in humans. During pregnancy, urinary tract infect... more The urinary tract is a common site of infection in humans. During pregnancy, urinary tract infection (UTI) is associated with increased risks of maternal and neonatal morbidity and mortality, even when the infection is asymptomatic. By mapping available rates of UTI in pregnancy across different populations, we emphasize this as a problem of global significance. Many countries with high rates of preterm birth and neonatal mortality also have rates of UTI in pregnancy that exceed rates seen in more developed countries. A global analysis of the etiologies of UTI revealed familiar culprits as well as emerging threats. Screening and treatment of UTI have improved birth outcomes in several more developed countries and would likely improve maternal and neonatal health worldwide. However, challenges of implementation in resource-poor settings must be overcome. We review the nature of the barriers occurring at each step of the screening and treatment pipeline and highlight steps necessary t...
Covalent bond formation to proteins is made difficult by their multiple unprotected functional gr... more Covalent bond formation to proteins is made difficult by their multiple unprotected functional groups and normally low concentrations. A water-soluble sulfonated bathophenanthroline ligand (2) was used to promote a highly efficient Cu(I)-mediated azide-alkyne cycloaddition (CuAAC) reaction for the chemoselective attachment of biologically relevant molecules to cowpea mosaic virus (CPMV). The ligated substrates included complex sugars, peptides, poly(ethylene oxide) polymers, and the iron carrier protein transferrin, with routine success even for cases that were previously resistant to azide-alkyne coupling using the conventional ligand tris(triazolyl)amine (1). The use of 4-6 equiv of substrate was sufficient to achieve loadings of 60-115 molecules/virion in yields of 60-85%. Although it is sensitive to oxygen, the reliably efficient performance of the Cu.2 system makes it a useful tool for demanding bioconjugation applications.
Journal of the American Chemical Society, Jan 4, 2004
Copper-based catalysts for the 1,3-dipolar cycloaddition of azides and alkynes were screened in p... more Copper-based catalysts for the 1,3-dipolar cycloaddition of azides and alkynes were screened in parallel fashion using a fluorescence quenching assay. The method was designed to identify systems able to accelerate the coupling of reactants at micromolar concentrations in aqueous mixtures and to obtain quantitative comparisons of their activities. In addition to the tris(triazolylamines) previously reported, two types of compounds (bipy/phen and 2-pyridyl Schiff bases) were found to exhibit significant ligand-accelerated catalysis, with one complex showing especially dramatic rate enhancements. Preliminary explorations of the dependence of reaction rate on pH, ligand:Cu ratio, and Cu concentration are described.
Virtually all cells in the body have an intracellular clockwork based on a negative feedback mech... more Virtually all cells in the body have an intracellular clockwork based on a negative feedback mechanism. The circadian timekeeping system in mammals is a hierarchical multi-oscillator network, with the suprachiasmatic nuclei (SCN) acting as the central pacemaker. The SCN synchronizes to daily light-dark cycles and coordinates rhythmic physiology and behavior. Synchronization in the SCN and at the organismal level is a key feature of the circadian clock system. In particular, intercellular coupling in the SCN synchronizes neuron oscillators and confers robustness against perturbations. Recent advances in our knowledge of and ability to manipulate circadian rhythms make available cell-based clock models, which lack strong coupling and are ideal for target discovery and chemical biology.
Desorption/ionization on silicon mass spectrometry (DIOS-MS) is a matrix-less laser vaporization ... more Desorption/ionization on silicon mass spectrometry (DIOS-MS) is a matrix-less laser vaporization method for generating gas-phase ions. The physical properties of the silicon surfaces are crucial to DIOS-MS performance and are controlled by the selection of silicon type and the silicon etching conditions. DIOS-MS has been examined for its applicability to small-molecule analysis, quantitative studies, reaction monitoring, chromatography, protein identification, and
... David D. Dıaz, Warren G. Lewis, and MG Finnà Department of Chemistry and The Skaggs Institute... more ... David D. Dıaz, Warren G. Lewis, and MG Finnà Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute ... Bull., 49, 933 (2001); A. Donetti, E. Cereda, E. Bellora, A. Gallazzi, C. Bazzano, P. Vanoni, P. Del Soldato, R. Micheletti, F ...
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