The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Barry Gold - One of the best experts on this subject based on the ideXlab platform.
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DNA damage and cytotoxicity induced by minor groove binding Methyl Sulfonate esters.
Biochemistry, 2003Co-Authors: Sridhar Varadarajan, Prasad Dande, Dharini Shah, Fa Xian Chen, Samuel Settles, Gilberto Fronza, Barry GoldAbstract:Minor groove specific DNA equilibrium binding peptides (lex) based on N-Methylpyrrole-carboxamide and/or N-Methylimidazolecarboxamide subunits have been modified with an O-Methyl Sulfonate ester functionality to target DNA Methylation in the minor groove at Ade/Thy- and/or Gua/Cyt-rich sequences. HPLC and sequencing gel analyses show that the Me-lex compounds all selectively react with DNA to afford N3-alkyladenine as a major adduct. The formation of the N3-alkyladenine lesions is sequence-dependent based on the equilibrium binding preferences of the different lex peptides. In addition to the reaction at adenine, the molecules designed to target Gua/Cyt sequences also generate lesions at guanine; however, the Methylation is not sequence dependent and takes places in the major groove at the N7-position. To determine if and how the level of the different DNA adducts and the sequence selectivity for their formation affects cytotoxicity, the Me-lex analogues were tested in wild type Escherichia coli and in mu...
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DNA damage and cytotoxicity induced by minor groove binding Methyl Sulfonate esters.
Biochemistry, 2003Co-Authors: Sridhar Varadarajan, Prasad Dande, Dharini Shah, Fa Xian Chen, Samuel Settles, Gilberto Fronza, Barry GoldAbstract:Minor groove specific DNA equilibrium binding peptides (lex) based on N-Methylpyrrole-carboxamide and/or N-Methylimidazolecarboxamide subunits have been modified with an O-Methyl Sulfonate ester functionality to target DNA Methylation in the minor groove at Ade/Thy- and/or Gua/Cyt-rich sequences. HPLC and sequencing gel analyses show that the Me-lex compounds all selectively react with DNA to afford N3-alkyladenine as a major adduct. The formation of the N3-alkyladenine lesions is sequence-dependent based on the equilibrium binding preferences of the different lex peptides. In addition to the reaction at adenine, the molecules designed to target Gua/Cyt sequences also generate lesions at guanine; however, the Methylation is not sequence dependent and takes places in the major groove at the N7-position. To determine if and how the level of the different DNA adducts and the sequence selectivity for their formation affects cytotoxicity, the Me-lex analogues were tested in wild type Escherichia coli and in mutant strains defective in base excision repair (tag and/or alkA or apn). The results demonstrate the importance of 3-Methyladenine, and in some cases 3-Methylguanine, lesions in cellular toxicity, and the dominant protective role of the DNA glycosylases. There is no evidence that the sequence specificity is related to toxicity.
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evidence in escherichia coli that n3 Methyladenine lesions and cytotoxicity induced by a minor groove binding Methyl Sulfonate ester can be modulated in vivo by netropsin
Biochemistry, 2003Co-Authors: Dharini Shah, Barry GoldAbstract:The use of DNA equilibrium binding molecules to transfer alkyl groups to specific positions on DNA is an approach to generating cytotoxic DNA damage while avoiding the formation of promutagenic lesions that increase the risk for the development of secondary cancer. We have previously reported that in vitro a neutral DNA equilibrium binding agent based on an N-Methylpyrrolecarboxamide dipeptide (lex) and modified with an O-Methyl Sulfonate ester functionality (Me-lex) selectively affords N3-Methyladenine lesions in >90% yield relative to the formation of other adducts. While in vitro interactions between the lex dipeptide and DNA have been thoroughly studied, in vivo interactions are more difficult to elucidate. We report herein the relationship between the in vivo formation of N3-Methyladenine and toxicity in wild-type and base excision repair defective mutant Escherichia coli. In addition, it is demonstrated that both N3-Methyladenine adduction and cytotoxicity can be inhibited in vivo with netropsin, a potent competitive inhibitor of binding of lex to DNA. The results show a clear relationship between the levels of N3-Methyladenine and toxicity in an alkA/tag glycosylase mutant that cannot remove the adduct from its genome. For Methyl methaneSulfonate, which does not sequence selectively Methylate DNA, a relationship between the formation of N3-Methyladenine and toxicity is also observed. However, netropsin affects neither the level of N3-Methyladenine nor the toxicity of Methyl methaneSulfonate in E. coli.
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poly adp ribose polymerase inhibitor increases apoptosis and reduces necrosis induced by a dna minor groove binding Methyl Sulfonate ester
Cell Death & Differentiation, 2001Co-Authors: Lucio Tentori, Ilaria Portarena, Lauretta Levati, Enzo Bonmassar, Paola Vernole, Barry Gold, Alessandra Balduzzi, Grazia GrazianiAbstract:Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis induced by a DNA minor groove binding Methyl Sulfonate ester
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cytotoxic and clastogenic effects of a dna minor groove binding Methyl Sulfonate ester in mismatch repair deficient leukemic cells
Leukemia, 2000Co-Authors: Lucio Tentori, R Madaio, Ilaria Portarena, Lauretta Levati, Prasad Dande, Pedro Miguel Lacal, Mario Turriziani, Paola Vernole, Alessandra Balduzzi, Barry GoldAbstract:Cytotoxic and clastogenic effects of a DNA minor groove binding Methyl Sulfonate ester in mismatch repair deficient leukemic cells
Kay Saalwächter - One of the best experts on this subject based on the ideXlab platform.
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Intermediate motions and dipolar couplings as studied by Lee-Goldburg cross-polarization NMR: Hartmann-Hahn matching profiles.
Physical chemistry chemical physics : PCCP, 2009Co-Authors: Marcio Fernando Cobo, Detlef Reichert, Kay Saalwächter, Kateřina Maliňáková, Eduardo R. DeazevedoAbstract:In this article, we evaluate the use of simple Lee–Goldburg cross-polarization (LG-CP) NMR experiments for obtaining quantitative information of molecular motion in the intermediate regime. In particular, we introduce the measurement of Hartmann–Hahn matching profiles for the assessment of heteronuclear dipolar couplings as well as dynamics as a reliable and robust alternative to the more common analysis of build-up curves. We have carried out dynamic spin dynamics simulations in order to test the method’s sensitivity to intermediate motion and address its limitations concerning possible experimental imperfections. We further demonstrate the successful use of simple theoretical concepts, most prominently Anderson–Weiss (AW) theory, to analyze the data. We further propose an alternative way to estimate activation energies of molecular motions, based upon the acquisition of only two LG-CP spectra per temperature at different temperatures. As experimental tests, molecular jumps in imidazole Methyl Sulfonate, triMethylsulfoxonium iodide, and bisphenol A polycarbonate were investigated with the new method.
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Intermediate motions as studied by solid-state separated local field NMR experiments.
The Journal of chemical physics, 2008Co-Authors: Eduardo R. Deazevedo, Kay Saalwächter, Ovidiu Pascui, Andre Souza, Tito José Bonagamba, Detlef ReichertAbstract:In this report, the application of a class of separated local field NMR experiments named dipolar chemical shift correlation (DIPSHIFT) for probing motions in the intermediate regime is discussed. Simple analytical procedures based on the Anderson-Weiss (AW) approximation are presented. In order to establish limits of validity of the AW based formulas, a comparison with spin dynamics simulations based on the solution of the stochastic Liouville-von-Neumann equation is presented. It is shown that at short evolution times (less than 30% of the rotor period), the AW based formulas are suitable for fitting the DIPSHIFT curves and extracting kinetic parameters even in the case of jumplike motions. However, full spin dynamics simulations provide a more reliable treatment and extend the frequency range of the molecular motions accessible by DIPSHIFT experiments. As an experimental test, molecular jumps of imidazol Methyl Sulfonate and triMethylsulfoxonium iodide, as well as the side-chain motions in the photoluminescent polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene], were characterized. Possible extensions are also discussed.
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Solid state NMR spectroscopic investigations of model compounds for imidazole-based proton conductors
The Journal of Physical Chemistry B, 2004Co-Authors: Ingrid Fischbach, Kay Saalwächter, Hans Wolfgang Spiess, Gillian R. GowardAbstract:The temperature dependence and the exact geometry of slow molecular reorientations in imidazolium Methyl Sulfonate are investigated using modern one-dimensional MAS exchange spectroscopy. Earlier high-temperature studies have evidenced a fast 180° flip motion of the imidazole ring, which is shown here to slow on cooling and is believed to be a prototypical molecular process involved in Grotthus-type proton transport in imidazole-based proton conductors intended for fuel cell applications. It is further shown that valuable information on the relative orientations of CH and NH dipolar coupling tensors with respect to the chemical shift anisotropy tensors of the respective heteronuclei can be obtained from the MAS exchange data as well as from static 13C and 15N line shapes, without the necessity of performing more involved single-crystal NMR experiments. The principal axes of the CSA tensors are found to not coincide with the CH or NH bond axes, in contrast to earlier assumptions involving similar compounds...
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Reorientation phenomena in imidazolium Methyl Sulfonate as probed by advanced solid-state NMR.
Solid state nuclear magnetic resonance, 2003Co-Authors: Gillian R. Goward, Kay Saalwächter, Ingrid Fischbach, Hans Wolfgang SpiessAbstract:Abstract Evidence for reorientation of imidazolium rings in imidazolium MethylSulfonate is demonstrated using solid-state NMR. This material is a model system for exciting new proton-conducting materials based on imidazole. Two advanced NMR methods, including 1 H– 13 C and 1 H– 15 N recoupled polarization transfer with dipolar sideband pattern analysis and analysis of the coalescence of 13 C lineshapes are used to characterize the ring reorientation. The process is found to occur at temperatures well below the melting point of the salt, between 240 and 380 K, and is described by a single activation energy, of 38±5 kJ/mol. This material is considered as a model system for quantifying the ring reorientation process, which is often proposed to be the rate-limiting step in proton transport in imidazole-based proton conducting materials.
Hans Wolfgang Spiess - One of the best experts on this subject based on the ideXlab platform.
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Solid state NMR spectroscopic investigations of model compounds for imidazole-based proton conductors
The Journal of Physical Chemistry B, 2004Co-Authors: Ingrid Fischbach, Kay Saalwächter, Hans Wolfgang Spiess, Gillian R. GowardAbstract:The temperature dependence and the exact geometry of slow molecular reorientations in imidazolium Methyl Sulfonate are investigated using modern one-dimensional MAS exchange spectroscopy. Earlier high-temperature studies have evidenced a fast 180° flip motion of the imidazole ring, which is shown here to slow on cooling and is believed to be a prototypical molecular process involved in Grotthus-type proton transport in imidazole-based proton conductors intended for fuel cell applications. It is further shown that valuable information on the relative orientations of CH and NH dipolar coupling tensors with respect to the chemical shift anisotropy tensors of the respective heteronuclei can be obtained from the MAS exchange data as well as from static 13C and 15N line shapes, without the necessity of performing more involved single-crystal NMR experiments. The principal axes of the CSA tensors are found to not coincide with the CH or NH bond axes, in contrast to earlier assumptions involving similar compounds...
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Reorientation phenomena in imidazolium Methyl Sulfonate as probed by advanced solid-state NMR.
Solid state nuclear magnetic resonance, 2003Co-Authors: Gillian R. Goward, Kay Saalwächter, Ingrid Fischbach, Hans Wolfgang SpiessAbstract:Abstract Evidence for reorientation of imidazolium rings in imidazolium MethylSulfonate is demonstrated using solid-state NMR. This material is a model system for exciting new proton-conducting materials based on imidazole. Two advanced NMR methods, including 1 H– 13 C and 1 H– 15 N recoupled polarization transfer with dipolar sideband pattern analysis and analysis of the coalescence of 13 C lineshapes are used to characterize the ring reorientation. The process is found to occur at temperatures well below the melting point of the salt, between 240 and 380 K, and is described by a single activation energy, of 38±5 kJ/mol. This material is considered as a model system for quantifying the ring reorientation process, which is often proposed to be the rate-limiting step in proton transport in imidazole-based proton conducting materials.
Gillian R. Goward - One of the best experts on this subject based on the ideXlab platform.
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Solid state NMR spectroscopic investigations of model compounds for imidazole-based proton conductors
The Journal of Physical Chemistry B, 2004Co-Authors: Ingrid Fischbach, Kay Saalwächter, Hans Wolfgang Spiess, Gillian R. GowardAbstract:The temperature dependence and the exact geometry of slow molecular reorientations in imidazolium Methyl Sulfonate are investigated using modern one-dimensional MAS exchange spectroscopy. Earlier high-temperature studies have evidenced a fast 180° flip motion of the imidazole ring, which is shown here to slow on cooling and is believed to be a prototypical molecular process involved in Grotthus-type proton transport in imidazole-based proton conductors intended for fuel cell applications. It is further shown that valuable information on the relative orientations of CH and NH dipolar coupling tensors with respect to the chemical shift anisotropy tensors of the respective heteronuclei can be obtained from the MAS exchange data as well as from static 13C and 15N line shapes, without the necessity of performing more involved single-crystal NMR experiments. The principal axes of the CSA tensors are found to not coincide with the CH or NH bond axes, in contrast to earlier assumptions involving similar compounds...
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Reorientation phenomena in imidazolium Methyl Sulfonate as probed by advanced solid-state NMR.
Solid state nuclear magnetic resonance, 2003Co-Authors: Gillian R. Goward, Kay Saalwächter, Ingrid Fischbach, Hans Wolfgang SpiessAbstract:Abstract Evidence for reorientation of imidazolium rings in imidazolium MethylSulfonate is demonstrated using solid-state NMR. This material is a model system for exciting new proton-conducting materials based on imidazole. Two advanced NMR methods, including 1 H– 13 C and 1 H– 15 N recoupled polarization transfer with dipolar sideband pattern analysis and analysis of the coalescence of 13 C lineshapes are used to characterize the ring reorientation. The process is found to occur at temperatures well below the melting point of the salt, between 240 and 380 K, and is described by a single activation energy, of 38±5 kJ/mol. This material is considered as a model system for quantifying the ring reorientation process, which is often proposed to be the rate-limiting step in proton transport in imidazole-based proton conducting materials.
Ingrid Fischbach - One of the best experts on this subject based on the ideXlab platform.
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Solid state NMR spectroscopic investigations of model compounds for imidazole-based proton conductors
The Journal of Physical Chemistry B, 2004Co-Authors: Ingrid Fischbach, Kay Saalwächter, Hans Wolfgang Spiess, Gillian R. GowardAbstract:The temperature dependence and the exact geometry of slow molecular reorientations in imidazolium Methyl Sulfonate are investigated using modern one-dimensional MAS exchange spectroscopy. Earlier high-temperature studies have evidenced a fast 180° flip motion of the imidazole ring, which is shown here to slow on cooling and is believed to be a prototypical molecular process involved in Grotthus-type proton transport in imidazole-based proton conductors intended for fuel cell applications. It is further shown that valuable information on the relative orientations of CH and NH dipolar coupling tensors with respect to the chemical shift anisotropy tensors of the respective heteronuclei can be obtained from the MAS exchange data as well as from static 13C and 15N line shapes, without the necessity of performing more involved single-crystal NMR experiments. The principal axes of the CSA tensors are found to not coincide with the CH or NH bond axes, in contrast to earlier assumptions involving similar compounds...
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Reorientation phenomena in imidazolium Methyl Sulfonate as probed by advanced solid-state NMR.
Solid state nuclear magnetic resonance, 2003Co-Authors: Gillian R. Goward, Kay Saalwächter, Ingrid Fischbach, Hans Wolfgang SpiessAbstract:Abstract Evidence for reorientation of imidazolium rings in imidazolium MethylSulfonate is demonstrated using solid-state NMR. This material is a model system for exciting new proton-conducting materials based on imidazole. Two advanced NMR methods, including 1 H– 13 C and 1 H– 15 N recoupled polarization transfer with dipolar sideband pattern analysis and analysis of the coalescence of 13 C lineshapes are used to characterize the ring reorientation. The process is found to occur at temperatures well below the melting point of the salt, between 240 and 380 K, and is described by a single activation energy, of 38±5 kJ/mol. This material is considered as a model system for quantifying the ring reorientation process, which is often proposed to be the rate-limiting step in proton transport in imidazole-based proton conducting materials.