The Experts below are selected from a list of 183 Experts worldwide ranked by ideXlab platform
Gopinatha Suresh Kumar - One of the best experts on this subject based on the ideXlab platform.
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Design and synthesis of a sulphur containing Schiff base Drug: DNA Binding studies and theoretical calculations.
Journal of Biomolecular Structure & Dynamics, 2020Co-Authors: Urmila Saha, Gopinatha Suresh Kumar, Malay Dolai, Saugata Konar, Ray J. Butcher, Subrata MukhopadhyayAbstract:AbstractThe Schiff base compound MTA ((E)-5-methyl-N'-((5-methylthiophen-2-yl)methylene)-1H-pyrazole-3-carbohydrazide) derived from 2-thiophenecarboxaldehyde and 5-methylpyrazole-3-carbohydrazide h...
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Drug DNA Binding thermodynamics a comparative study of aristololactam β d glucoside and daunomycin
The Journal of Chemical Thermodynamics, 2012Co-Authors: Gopinatha Suresh KumarAbstract:Abstract Thermal melting and microcalorimetric studies have been carried out to investigate and compare the thermodynamics of interaction of two sugars bearing Drugs viz. the aristololactam-β- d -glucoside (ADG) and daunomycin (DAU) with DNA. Both compounds stabilized DNA against thermal strand separation but daunomycin promoted a much higher stability compared to ADG. The Binding affinity of ADG was of the order of 10 5 M −1 while that of daunomycin was higher by one order (10 6 M −1 ). There is only one class of Binding site on DNA for both ADG and DAU. The Binding was predominantly enthalpy driven for both compounds but the entropy contribution was different. Although higher salt concentration decreased the Binding affinity in both cases the variation was higher for DAU compared to ADG. Temperature dependent calorimetric data suggested that the enthalpy and entropy changes reduced but compensated each other to keep the Gibbs free energy change almost same and gave negative Δ C p ∘ values. The complexation of both Drugs to DNA appears to be similar with higher affinity for DAU over ADG but the energetics are different. DAU is a better DNA intercalator compared to ADG.
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Drug–DNA Binding thermodynamics: A comparative study of aristololactam-β-d-glucoside and daunomycin
The Journal of Chemical Thermodynamics, 2012Co-Authors: Gopinatha Suresh KumarAbstract:Abstract Thermal melting and microcalorimetric studies have been carried out to investigate and compare the thermodynamics of interaction of two sugars bearing Drugs viz. the aristololactam-β- d -glucoside (ADG) and daunomycin (DAU) with DNA. Both compounds stabilized DNA against thermal strand separation but daunomycin promoted a much higher stability compared to ADG. The Binding affinity of ADG was of the order of 10 5 M −1 while that of daunomycin was higher by one order (10 6 M −1 ). There is only one class of Binding site on DNA for both ADG and DAU. The Binding was predominantly enthalpy driven for both compounds but the entropy contribution was different. Although higher salt concentration decreased the Binding affinity in both cases the variation was higher for DAU compared to ADG. Temperature dependent calorimetric data suggested that the enthalpy and entropy changes reduced but compensated each other to keep the Gibbs free energy change almost same and gave negative Δ C p ∘ values. The complexation of both Drugs to DNA appears to be similar with higher affinity for DAU over ADG but the energetics are different. DAU is a better DNA intercalator compared to ADG.
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Biophysical studies of mutated K562 DNA (erythroleukemic cells) Binding to adriamycin and daunomycin reveal that mutations induce structural changes influencing Binding behavior
Journal of Biomolecular Structure & Dynamics, 2012Co-Authors: Debjani Ghosh, Chabita Saha, Maidul Hossain, Gopinatha Suresh KumarAbstract:K562 cells are erythroleukemic cells derived from a chronic myeloid leukemia patient in blast crisis. Comparison of the genome from K562 cells and normal human genome has been very useful strategy, in uncovering eight genes, implicated in acute myeloid leukemia (AML). These genes carry mutations in K562 genome and the role of these mutations in the progression and treatment of AML is still not known. Consequences of these mutations on Drug DNA Binding are also not known exactly. In the present study, mutation induced structural changes in K562 genome, compared to normal genome, are identified by Fourier transform infra red (FTIR) and circular dichroism (CD) spectroscopy. These structural changes in native K562 DNA favor stronger Binding with Binding constants 2.0 × 108 and 1.9 × 109 M−1 with antileukemic Drugs adriamycin and daunomycin (DNM), respectively, compared to normal DNA. On Binding, these Drugs disrupt the native B form structure of normal DNA to a greater extent, compared to A-like structure of ...
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molecular aspects on the interaction of phenosafranine to deoxyribonucleic acid model for intercalative Drug DNA Binding
Journal of Molecular Structure, 2008Co-Authors: Gopinatha Suresh KumarAbstract:Abstract The mode, mechanism and energetics of interaction of phenosafranine, the planar, cationic and rigid phenazium dye to calf thymus DNA was investigated from absorption, fluorescence, circular dichroism, isothermal titration calorimetry, thermal melting, and viscosity. The study revealed non-cooperative Binding of the dye to DNA with an affinity in the range (3.81–4.22) × 105 M−1 as observed from diverse techniques and obeying neighbor exclusion principle. The stoichiometry of Binding was characterized to be one phenosafranine molecule per two base pairs. The Binding was characterized by strong stabilization of DNA against thermal strand separation, large intrinsic circular dichroic changes of DNA by itself and the generation of induced circular dichroism for the optically inactive phenosafranine molecules. Hydrodynamic and fluorescence quenching studies revealed strong evidence that the phenosafranine molecules are intercalated between every alternate base pairs of calf thymus DNA. Isothermal titration calorimetry studies suggested that the Binding was exothermic and favoured by both negative enthalpy and positive entropy changes. This study for the first time presents the complete molecular aspects and energetics of phenosafranine complexation to DNA as model for intercalative Drug–DNA interaction.
Jonathan B Chaires - One of the best experts on this subject based on the ideXlab platform.
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a thermodynamic signature for Drug DNA Binding mode
Archives of Biochemistry and Biophysics, 2006Co-Authors: Jonathan B ChairesAbstract:Abstract A number of small molecules bind directly and selectively to DNA, acting as chemotherapeutic agents by inhibiting replication, transcription or topoisomerase activity. Two common Binding modes for these small molecules are intercalation or groove-Binding. Intercalation results from insertion of a planar aromatic substituent between DNA base pairs, with concomitant unwinding and lengthening of the DNA helix. Groove Binding, in contrast, does not perturb the duplex structure to any great extent. Groove-binders are typically crescent-shaped, and fit snugly into the minor groove with little distortion of the DNA structure. Recent calorimetric studies have determined the enthalpic and entropic contributions to the DNA Binding of representative DNA Binding compounds. Analysis of such thermodynamic data culled from the literature reveals distinctive thermodynamic signatures for groove-Binding and intercalating compounds. Plots of the Binding enthalpy (Δ H ) against Binding entropy (− T Δ S ) for 26 Drug–DNA interactions reveal that groove-Binding interactions are clustered in a region of the graph with favorable entropy contributions to the free energy, while intercalators are clustered in a region with unfavorable entropy but favorable enthalpy contributions. Groove-Binding is predominantly entropically driven, while intercalation in enthalpically driven. The molecular basis of the contrasting thermodynamic signatures for the two Binding modes is by no means clear, but the pattern should be of use in categorizing new DNA Binding agents.
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analysis of Drug DNA Binding data
Methods in Enzymology, 2000Co-Authors: Xiaogang Qu, Jonathan B ChairesAbstract:Publisher Summary This chapter discusses the analysis of Drug-DNA Binding data. This chapter describes the protocols for the numerical analysis of primary fluorescence and absorbance titration data that have evolved during the past decade. The rational design of new DNA Binding agents requires a thorough understanding of the thermodynamics of the DNA Binding of the existing Drugs. Fundamental to any thermodynamic characterization of the Drug–DNA interactions is the determination of Binding constants. Because many DNA Binding Drugs exhibit large changes in absorbance or fluorescence on Binding, these changes are commonly used to determine the distribution of free and bound Drug in solution to construct Binding isotherms that may be used to obtain Binding constants. Fluorescence and absorbance spectroscopies provide a powerful means of determining Drug–DNA Binding constants. In addition, the chapter also describes the application of nonlinear least squares fitting methods, coupled with Monte Carlo analysis, to reliably estimate limiting optical parameters and their errors that are necessary to compute the distribution of free and bound ligand from spectroscopic data.
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Energetics of Drug–DNA interactions
Biopolymers, 1997Co-Authors: Jonathan B ChairesAbstract:Understanding the thermodynamics of Drug Binding to DNA is of both practical and fundamental interest. The practical interest lies in the contribution that thermodynamics can make to the rational design process for the development of new DNA targeted Drugs. Thermodynamics offer key insights into the molecular forces that drive complex formation that cannot be obtained by structural or computational studies alone. The fundamental interest in these interactions lies in what they can reveal about the general problems of parsing and predicting ligand Binding free energies. For these problems, Drug–DNA interactions offer several distinct advantages, among them being that the structures of many Drug–DNA complexes are known at high resolution and that such structures reveal that in many cases the Drug acts as a rigid body, with little conformational change upon Binding. Complete thermodynamic profiles (ΔG, ΔH, ΔS, ΔCp) for numerous Drug–DNA interactions have been obtained, with the help of high-sensitivity microcalorimetry. The purpose of this article is to offer a perspective on the interpretation of these thermodynamics parameters, and in particular how they might be correlated with known structural features. Obligatory conformational changes in the DNA to accommodate intercalators and the loss of translational and rotational freedom upon complex formation both present unfavorable free energy barriers for Binding. Such barriers must be overcome by favorable free energy contributions from the hydrophobic transfer of ligand from solution into the Binding site, polyelectrolyte contributions from coupled ion release, and molecular interactions (hydrogen and ionic bonds, van der Waals interactions) that form within the Binding site. Theoretical and semiempirical tools that allow estimates of these contributions to be made will be discussed, and their use in dissecting experimental data illustrated. This process, even at the current level of approximation, can shed considerable light on the Drug-DNA Binding process. © 1998 John Wiley & Sons, Inc. Biopoly 44: 201–215, 1997
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Analysis of Drug-DNA Binding isotherms: a Monte Carlo approach.
Methods in Enzymology, 1994Co-Authors: John J. Correia, Jonathan B ChairesAbstract:Publisher Summary A number of medically important antibiotics exert their influence by direct interaction with cellular DNA and subsequent inhibition of replication and transcription. A fundamental step in understanding the moelcular mechanism of antibiotic action in these cases is the characterization of their equilibrium Binding to DNA. The neighbor exclusion models have been commonly used to interpret and analyze such antibiotic–DNA Binding isotherms. These models evolved because of complicating features unique to ligand Binding to the linear DNA lattice. This chapter discusses the practical numerical aspects of using neighbor exclusion models and nonlinear least squares fitting techniques to extract quantitative data from experimental Binding isotherms. McGhee and von Hippel used a simple combinatorial approach to arrive at closed form equations that embodied the neighbor exclusion principle and which could be readily incorporated into nonlinear least squares fitting routines. These equations are widely used for data analysis. In addition to neighbor exclusion behavior, McGhee and von Hippel introduced an additional parameter to account for cooperative interactions between ligands on the DNA lattice.
Ekaterina A Korobkova - One of the best experts on this subject based on the ideXlab platform.
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determination of the Drug DNA Binding modes using fluorescence based assays
Analytical Biochemistry, 2012Co-Authors: Alicia K Williams, Sofia Cheliout Dasilva, Ankit Bhatta, Baibhav Rawal, Ekaterina A KorobkovaAbstract:Abstract Therapeutic Drugs and environmental pollutants may exhibit high reactivity toward DNA bases and backbone. Understanding the mechanisms of Drug–DNA Binding is crucial for predicting their potential genotoxicity. We developed a fluorescence analytical method for the determination of the preferential Binding mode for Drug–DNA interactions. Two nucleic acid dyes were employed in the method: TO-PRO-3 iodide (TP3) and 4′,6-diamidino-2-phenylindole (DAPI). TP3 binds DNA by intercalation, whereas DAPI exhibits minor groove Binding. Both dyes exhibit significant fluorescence magnification on Binding to DNA. We evaluated the DNA Binding constant, Kb, for each dye. We also performed fluorescence quenching experiments with 11 molecules of various structures and measured a C50 value for each compound. We determined preferential Binding modes for the aforementioned molecules and found that they bound to DNA consistently, as indicated by other studies. The values of the likelihood of DNA intercalation were correlated with the partition coefficients of the molecules. In addition, we performed nuclear magnetic resonance (NMR) studies of the interactions with calf thymus DNA for the three molecules. The results were consistent with the fluorescence method described above. Thus, we conclude that the fluorescence method we developed provides a reliable determination of the likelihoods of the two different DNA Binding modes.
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Determination of the Drug–DNA Binding modes using fluorescence-based assays
Analytical Biochemistry, 2012Co-Authors: Alicia K Williams, Sofia Cheliout Dasilva, Ankit Bhatta, Baibhav Rawal, Ekaterina A KorobkovaAbstract:Abstract Therapeutic Drugs and environmental pollutants may exhibit high reactivity toward DNA bases and backbone. Understanding the mechanisms of Drug–DNA Binding is crucial for predicting their potential genotoxicity. We developed a fluorescence analytical method for the determination of the preferential Binding mode for Drug–DNA interactions. Two nucleic acid dyes were employed in the method: TO-PRO-3 iodide (TP3) and 4′,6-diamidino-2-phenylindole (DAPI). TP3 binds DNA by intercalation, whereas DAPI exhibits minor groove Binding. Both dyes exhibit significant fluorescence magnification on Binding to DNA. We evaluated the DNA Binding constant, Kb, for each dye. We also performed fluorescence quenching experiments with 11 molecules of various structures and measured a C50 value for each compound. We determined preferential Binding modes for the aforementioned molecules and found that they bound to DNA consistently, as indicated by other studies. The values of the likelihood of DNA intercalation were correlated with the partition coefficients of the molecules. In addition, we performed nuclear magnetic resonance (NMR) studies of the interactions with calf thymus DNA for the three molecules. The results were consistent with the fluorescence method described above. Thus, we conclude that the fluorescence method we developed provides a reliable determination of the likelihoods of the two different DNA Binding modes.
Alicia K Williams - One of the best experts on this subject based on the ideXlab platform.
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determination of the Drug DNA Binding modes using fluorescence based assays
Analytical Biochemistry, 2012Co-Authors: Alicia K Williams, Sofia Cheliout Dasilva, Ankit Bhatta, Baibhav Rawal, Ekaterina A KorobkovaAbstract:Abstract Therapeutic Drugs and environmental pollutants may exhibit high reactivity toward DNA bases and backbone. Understanding the mechanisms of Drug–DNA Binding is crucial for predicting their potential genotoxicity. We developed a fluorescence analytical method for the determination of the preferential Binding mode for Drug–DNA interactions. Two nucleic acid dyes were employed in the method: TO-PRO-3 iodide (TP3) and 4′,6-diamidino-2-phenylindole (DAPI). TP3 binds DNA by intercalation, whereas DAPI exhibits minor groove Binding. Both dyes exhibit significant fluorescence magnification on Binding to DNA. We evaluated the DNA Binding constant, Kb, for each dye. We also performed fluorescence quenching experiments with 11 molecules of various structures and measured a C50 value for each compound. We determined preferential Binding modes for the aforementioned molecules and found that they bound to DNA consistently, as indicated by other studies. The values of the likelihood of DNA intercalation were correlated with the partition coefficients of the molecules. In addition, we performed nuclear magnetic resonance (NMR) studies of the interactions with calf thymus DNA for the three molecules. The results were consistent with the fluorescence method described above. Thus, we conclude that the fluorescence method we developed provides a reliable determination of the likelihoods of the two different DNA Binding modes.
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Determination of the Drug–DNA Binding modes using fluorescence-based assays
Analytical Biochemistry, 2012Co-Authors: Alicia K Williams, Sofia Cheliout Dasilva, Ankit Bhatta, Baibhav Rawal, Ekaterina A KorobkovaAbstract:Abstract Therapeutic Drugs and environmental pollutants may exhibit high reactivity toward DNA bases and backbone. Understanding the mechanisms of Drug–DNA Binding is crucial for predicting their potential genotoxicity. We developed a fluorescence analytical method for the determination of the preferential Binding mode for Drug–DNA interactions. Two nucleic acid dyes were employed in the method: TO-PRO-3 iodide (TP3) and 4′,6-diamidino-2-phenylindole (DAPI). TP3 binds DNA by intercalation, whereas DAPI exhibits minor groove Binding. Both dyes exhibit significant fluorescence magnification on Binding to DNA. We evaluated the DNA Binding constant, Kb, for each dye. We also performed fluorescence quenching experiments with 11 molecules of various structures and measured a C50 value for each compound. We determined preferential Binding modes for the aforementioned molecules and found that they bound to DNA consistently, as indicated by other studies. The values of the likelihood of DNA intercalation were correlated with the partition coefficients of the molecules. In addition, we performed nuclear magnetic resonance (NMR) studies of the interactions with calf thymus DNA for the three molecules. The results were consistent with the fluorescence method described above. Thus, we conclude that the fluorescence method we developed provides a reliable determination of the likelihoods of the two different DNA Binding modes.
Chabita Saha - One of the best experts on this subject based on the ideXlab platform.
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mutation induced conformational changes in genomic DNA from cancerous k562 cells influence Drug DNA Binding modes
PLOS ONE, 2014Co-Authors: Debjani Ghosh, Chabita SahaAbstract:Normal human genomic DNA (N-DNA) and mutated DNA (M-DNA) from K562 leukemic cells show different thermodynamic properties and Binding affinities on interaction with anticancer Drugs; adriamycin (ADR) and daunomycin (DNM). Isothermal calorimetric thermograms representing titration of ADR/DNM with N-DNA and M-DNA on analysis best fitted with sequential model of four and three events respectively. From Raman spectroscopy it has been identified that M-DNA is partially transformed to A form owing to mutations and N-DNA on Binding of Drugs too undergoes transition to A form of DNA. A correlation of thermodynamic contribution and structural data reveal the presence of different Binding events in Drug and DNA interactions. These events are assumed to be representative of minor groove complexation, reorientation of the Drug in the complex, DNA deformation to accommodate the Drugs and finally intercalation. Dynamic light scattering and zeta potential data also support differences in structure and mode of Binding of N and M DNA. This study highlights that mutations can manifest structural changes in DNA, which may influence the Binding efficacy of the Drugs. New generation of Drugs can be designed which recognize the difference in DNA structure in the cancerous cells instead of their biochemical manifestation.
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Biophysical studies of mutated K562 DNA (erythroleukemic cells) Binding to adriamycin and daunomycin reveal that mutations induce structural changes influencing Binding behavior
Journal of Biomolecular Structure & Dynamics, 2012Co-Authors: Debjani Ghosh, Chabita Saha, Maidul Hossain, Gopinatha Suresh KumarAbstract:K562 cells are erythroleukemic cells derived from a chronic myeloid leukemia patient in blast crisis. Comparison of the genome from K562 cells and normal human genome has been very useful strategy, in uncovering eight genes, implicated in acute myeloid leukemia (AML). These genes carry mutations in K562 genome and the role of these mutations in the progression and treatment of AML is still not known. Consequences of these mutations on Drug DNA Binding are also not known exactly. In the present study, mutation induced structural changes in K562 genome, compared to normal genome, are identified by Fourier transform infra red (FTIR) and circular dichroism (CD) spectroscopy. These structural changes in native K562 DNA favor stronger Binding with Binding constants 2.0 × 108 and 1.9 × 109 M−1 with antileukemic Drugs adriamycin and daunomycin (DNM), respectively, compared to normal DNA. On Binding, these Drugs disrupt the native B form structure of normal DNA to a greater extent, compared to A-like structure of ...
