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1.
The interaction mechanism and binding mode of capecitabine with ctDNA was extensively investigated using docking and molecular dynamics simulations, fluorescence and circular dichroism (CD) spectroscopy, DNA thermal denaturation studies, and viscosity measurements. The possible binding mode and acting forces on the combination between capecitabine and DNA had been predicted through molecular simulation. Results indicated that capecitabine could relatively locate stably in the G-C base-pairs-rich DNA minor groove by hydrogen bond and several weaker nonbonding forces. Fluorescence spectroscopy and fluorescence lifetime measurements confirmed that the quenching was static caused by ground state complex formation. This phenomenon indicated the formation of a complex between capecitabine and ctDNA. Fluorescence data showed that the binding constants of the complex were approximately 2 × 104 M?1. Calculated thermodynamic parameters suggested that hydrogen bond was the main force during binding, which were consistent with theoretical results. Moreover, CD spectroscopy, DNA melting studies, and viscosity measurements corroborated a groove binding mode of capecitabine with ctDNA. This binding had no effect on B-DNA conformation.  相似文献   

2.
    
Interaction of procarbazine (PCZ) with calf thymus DNA was studied using biophysical and molecular docking studies. Procarbazine was to interact with DNA with a binding constant of 6.52 × 103 M−1 as calculated using ultraviolet‐visible spectroscopy. To find out the binding mode, molecular docking was performed that predicted PCZ to interact with DNA through groove binding mode with binding affinity of −6.7 kcal/mole. To confirm the groove binding nature, different experiments were performed. Dye displacement assays confirmed the non‐intercalative binding mode. Procarbazine displaced Hoechst dye from the minor groove of DNA while it was unable to displace intercalating dyes. There was no increase in the viscosity of DNA solution in presence of PCZ. Also, negligible change in the secondary structure of DNA was observed in presence of PCZ as evident by circular dichroism spectra. Procarbazine caused decrease in the melting temperature of DNA possibly because of decrease in the stability of DNA caused by groove binding interaction of PCZ with DNA.  相似文献   

3.
In the present study, attempt was made to explore the interaction between biochanin-A (BioA) and calf thymus DNA (ctDNA) by employing fluorescence spectroscopy, absorption spectroscopy, circular dichroism (CD), DNA melting studies, viscosity measurements, and molecular modeling methods. A well-known fluorescence probe, acridine orange (AO) was used in the present study in order to enhance the emission intensity of weakly fluorescent ctDNA. Quenching in emission intensity of ctDNA-AO system was observed in the presence of different concentrations of BioA, suggesting that BioA has interacted with ctDNA. The hyperchromic effect observed upon the addition of BioA in the absorption spectra of ctDNA-AO without any shift in its absorption maximum revealed that BioA was bound to ctDNA through groove mode of binding. Further the groove mode of binding of BioA to ctDNA was confirmed by DNA melting studies, viscosity measurements, and molecular docking studies. The results of fluorescence measurements that were carried out at different temperature indicated that the BioA has quenched the emission intensity of ctDNA-AO through static mode of quenching mechanism. Thermodynamic parameters revealed that the BioA-ctDNA-AO system was stabilized by van der Waals forces and hydrogen bonding. The effect of binding of BioA on the conformation of ctDNA was examined by circular dichroism studies.  相似文献   

4.
Abstract

Ferulic acid (FA), a dietary phenolic acid compound, is proved to possess numerous biological activities. Hence, this study was devoted to explore the interaction between FA and calf thymus DNA (ctDNA) by UV???vis absorption, fluorescence, circular dichroism (CD) spectroscopy combined with multivariate curve resolution-alternating least-squares (MCR???ALS) and molecular docking studies. The concentration curves and the pure spectra of compositions (FA, ctDNA and FA???ctDNA complex) were obtained by MCR???ALS approach to verify and monitor the interaction of FA with ctDNA. The groove binding mode between FA and ctDNA was confirmed by the results of melting analysis, viscosity measurements, single-stranded DNA experiments, and competitive studies. The binding constant of FA???ctDNA complex was 4.87?×?104 L mol?1 at 298?K. The values of enthalpy (ΔH°) and entropy (ΔS°) changes in the interaction were ?16.24?kJ mol?1 and 35.02?J mol?1 K?1, respectively, indicating that the main binding forces were hydrogen bonds and hydrophobic interactions. The result of CD spectra suggested that a decrease in right-handed helicity of ctDNA was induced by FA and the DNA conformational transition from the B-form to the A-form. The results of docking indicated that FA binding with ctDNA in the minor groove. These findings may be conducive to understand the interaction mechanism of FA with ctDNA and the pharmacological effects of FA.

Communicated by Ramaswamy H. Sarma

  相似文献   

5.
    
Abstract

In this paper, we have studied the in vitro binding of neotame (NTM), an artificial sweetener, with native calf thymus DNA using different methods including spectrophotometric, spectrofluorometric, competition experiment, circular dichroism (CD), and viscosimetric techniques. From the spectrophotometric studies, the binding constant (Kb) of NTM-DNA was calculated to be 2?×?103 M?1. The quenching of the intrinsic fluorescence of NTM in the presence of DNA at different temperatures was also used to calculate binding constants (Kb) as well as corresponding number of binding sites (n). Moreover, the obtained results indicated that the quenching mechanism involves static quenching. By comparing the competitive fluorimetric studies with Hoechst 33258, as a known groove probe, and methylene blue, as a known intercalation probe, and iodide quenching experiments it was revealed that NTM strongly binds in the grooves of the DNA helix, which was further confirmed by CD and viscosimetric studies. In addition, a molecular docking method was employed to further investigate the binding interactions between NTM and DNA, and confirm the obtained results.  相似文献   

6.
    
The binding interaction of lovastatin with calf thymus DNA (ct‐DNA) was studied using UV/Vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results showed that there was an obvious binding interaction of lovastatin with ct‐DNA and the binding constant (Kb) was 5.60 × 103 M–1 at 298 K. In the binding process of lovastatin with ct‐DNA, the enthalpy change (ΔH0) and entropy change (ΔS0) were –24.9 kJ/mol and –12.0 J/mol/K, respectively, indicating that the main binding interaction forces were van der Waal's force and hydrogen bonding. The molecular docking results suggested that lovastatin preferred to bind on the minor groove of different B‐DNA fragments and the conformation change of lovastatin in the lovastatin–DNA complex was obviously observed, implying that the flexibility of lovastatin molecule plays an important role in the formation of the stable lovastatin–ct‐DNA complex. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

7.
    
The over‐use of antibiotics has caused a number of problems such as contamination of antibiotic residues and virus resistance, and therefore has attracted global attention. In this study, spectroscopic techniques and molecular docking were employed to predict conformational changes and binding interaction between two cephalosporins (cefaclor and cefixime) and calf thymus DNA (ctDNA). Fluorescence and UV–vis spectra suggested that static quenching was predominant and cephalosporin bound to the groove region of ctDNA. Binding parameters calculated by the Stern–Volmer and Scatchard equations showed that cephalosporin bound to ctDNA with a binding affinity in the order of 103 L mol?1. Thermodynamic parameters further indicated that the reaction was a spontaneous process driven by enthalpy and entropy, and that the main binding force was an electrostatic force. The effects of iodide, denaturant, thermal denaturation and pH on a cephalosporin–Hoechst–DNA complex were also studied, and the results confirmed that cephalosporin bound to the groove area of DNA. Finally, these results were further confirmed by molecular docking and electrochemical studies.  相似文献   

8.
    
Donepezil (DNP) is one of approved drugs to treat Alzheimer's disease (AD). However, the potential effect of DNP on DNA is still unclear. Therefore, the interaction of DNP with calf thymus DNA (DNA) was studied in vitro using spectroscopic and molecular docking methods. Steady‐state and transient fluorescence experiments showed that there was a clear binding interaction between DNP and DNA, resulting from DNP fluorescence being quenched using DNA. DNP and DNA have one binding site between them, and the binding constant (Kb) was 0.78 × 104 L·mol?1 at 298 K. In this binding process, hydrophobic force was the main interaction force, because enthalpy change (ΔH) and entropy change (ΔS) of DNP–DNA were 67.92 kJ·mol?1 and 302.96 J·mol?1·K?1, respectively. DNP bound to DNA in a groove‐binding mode, which was verified using a competition displacement study and other typical spectroscopic methods. Fourier transform infrared (FTIR) spectrum results showed that DNP interacted with guanine (G) and cytosine (C) bases of DNA. The molecular docking results further supported the results of spectroscopic experiments, and suggested that both Pi‐Sigma force and Pi‐Alkyl force were the major hydrophobic force functioning between DNP and DNA.  相似文献   

9.
In this report, we have investigated the binding affinity of tofacitinib with human serum albumin (HSA) under simulated physiological conditions by using UV–visible spectroscopy, fluorescence quenching measurements, dynamic light scattering (DLS), differential scanning calorimetry (DSC) and molecular docking methods. The obtained results demonstrate that fluorescence intensity of HSA gets quenched by tofacitinib and quenching occurs in static manner. Binding parameters calculated from modified Stern–Volmer equation shows that the drug binds to HSA with a binding constant in the order of 105. Synchronous fluorescence data deciphered the change in the microenvironment of tryptophan residue in HSA. UV spectroscopy and DLS measurements deciphered complex formation and reduction in hydrodynamic radii of the protein, respectively. Further DSC results show that tofacitinib increases the thermo stability of HSA. Hydrogen bonding and hydrophobic interaction are the main binding forces between HSA and tofacitinib as revealed by docking results.  相似文献   

10.
DNA-binding properties of an antiviral drug, valganciclovir (valcyte) was studied by using emission, absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, and computational studies. The drug bound to calf thymus DNA (ct-DNA) in a groove-binding mode. The calculated binding constant of UV-vis, Ka, is comparable to groove-binding drugs. Competitive fluorimetric studies with Hoechst 33258 showed that valcyte could displace the DNA-bound Hoechst 33258. The drug could not displace intercalated methylene blue from DNA double helix. Furthermore, the induced detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity confirm the groove-binding mode. In addition, an integrated molecular docking was employed to further investigate the binding interactions between valcyte and calf thymus DNA.  相似文献   

11.
Abstract

The binding characteristics of calf thymus DNA (ct-DNA) with dasatinib (DSTN), a tyrosine kinase inhibitor was assessed through multi-spectroscopic methodologies and viscosity measurement combined with molecular docking as well as DFT calculation to understand the binding mechanism, affinity of DSTN onto ct-DNA, effect of DSTN on ct-DNA conformation, and among others. The results confirmed DSTN bound onto ct-DNA, leading to forming the DSTN–ct-DNA complex with the binding constant of 4.82?×?103 M?1 at 310?K. DSTN preferentially inserted to the minor groove of ct-DNA with rich A-T region, that was the binding mode of DSTN onto ct-DNA was groove binding. The enthalpic change (ΔH0) and entropic change (ΔS0) during the binding process of DSTN with ct-DNA were 128.9?kJ mol?1 and 489.2?J mol?1 K?1, respectively, confirming clearly that the association of DSTN with ct-DNA was an endothermic process and the dominative driven-force was hydrophobic interaction. Meanwhile, the results also indicated that there was a certain extent of electrostatic force and hydrogen bonding, but they maybe play an auxiliary role. The CD measurement results confirmed the alteration in the helical configuration of ct-DNA but almost no change in the base stacking after binding DSTN. The results revealed that there was the obvious change in the conformation, the dipole moment, and the atomic charge distribution of DSTN in the B-DNA complexes, compared with free DSTN, to satisfy the conformational adaptation. From the obtained fronitier molecular orbitals of DSTN, it can be inferred that the nature of DSTN alters with the change of the environment around DSTN.

Communicated by Ramaswamy H. Sarma  相似文献   

12.
    
The thermodynamics of DNA‐ligand binding is important as it provides useful information to understand the details of binding processes. HIV‐1 REV response element (RRE) located in the env coding region of the viral genome is reported to be well conserved across different HIV‐1 isolates. In this study, the binding characteristics of Calf thymus DNA (ctDNA) and REV peptide from HIV‐1 were investigated using spectroscopic (UV–visible, fluorescence, and circular dichroism (CD)) and isothermal titration calorimetric (ITC) techniques. Thermal stability and ligand binding properties of the ctDNA revealed that native ctDNA had a T m of 75.5 °C, whereas the ctDNA–REV peptide complex exhibited an incremental shift in the T m by 8 °C, indicating thermal stability of the complex. CD data indicated increased ellipticity due to large conformational changes in ctDNA molecule upon binding with REV peptide and two binding stoichiometric modes are apparent. The ctDNA experienced condensation due to large conformational changes in the presence of REV peptide and positive B→Ψ transition was observed at higher molar charge ratios. Fluorescence studies performed at several ligand concentrations revealed a gradual decrease in the fluorescence intensity of EtBr‐bound ctDNA in response to increasing ligand concentrations. The fluorescence data further confirmed two stoichiometric modes of binding for ctDNA–REV peptide complex as previously observed with CD studies. The binding enthalpies were determined using ITC in the temperature range of 293 K–308 K. The ITC binding isotherm was exothermic at all temperatures examined, with low ΔH values indicating that the ctDNA–REV peptide interaction is driven largely by entropy. The heat capacity change (ΔC p) was insignificant, an unusual finding in the area of DNA‐peptide interaction studies. The variation in the values obtained for ΔH , ΔS , and ΔG with temperature further suggests that ctDNA–REV peptide interaction is entropically driven. ITC based analysis of salt dependence of binding constant gave a charge value (Z ) = +4.01, as determined for the δlnK /δln[Na+] parameter, suggesting the participation of only 3–4 Arg out of 11 Arg charge from REV peptide. The stoichiometry observed for the complex was three molar charge of REV peptide binding per molar charge of ctDNA. ITC based analysis further confirmed that the binding between ctDNA and REV peptide is governed by electrostatic interaction. Molecular interactions including H‐bonding, van der Waals forces, and solvent molecules rearrangement, underlie the binding of REV peptide to ctDNA.  相似文献   

13.
    
The purpose of this study was to explore an accurate characterization of the binding interaction of antibiotic drug cephalexin with calf thymus DNA (CT-DNA) as a relevant biological target by using UV absorption, fluorescence spectroscopy and circular dichroism (CD) in vitro under simulated physiological conditions (pH = 7.4) and also through a molecular modeling study. The results showed that the drug interacts with the DNA helix via a minor groove binding mode. The thermodynamic parameters were calculated and showed that the reaction between the drug and CT-DNA was exothermic. In addition, the drug enforced traceable changes in the viscosity of DNA. The molecular modeling results indicated that cephalexin forcefully binds to the minor groove of DNA with a relative binding energy of ?21.02?kJ mol?1. The obtained theoretical results were in good agreement with those obtained from experimental studies.  相似文献   

14.
The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 104 L mol?1 and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic. Circular dichroism spectroscopy was employed to measure the conformational change of DNA in the presence of cytarabine. Furthermore, the drug induces detectable changes in its viscosity for DNA interaction. The molecular modeling results illustrated that cytarabine strongly binds to groove of DNA by relative binding energy of docked structure ?20.61 KJ mol?1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the interaction of small molecular pollutants and drugs with biomacromolecules for clarifying the molecular mechanism of toxicity or side effect in vivo.  相似文献   

15.
The interaction of calf thymus DNA with nevirapine at physiological pH was studied by using absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, salt effect studies and computational methods. The drug binds to ct-DNA in a groove binding mode, as shown by slight variation in the viscosity of ct-DNA. Furthermore, competitive fluorimetric studies with Hoechst 33258 indicate that nevirapine binds to DNA via groove binding. Moreover, the structure of nevirapine was optimized by DFT calculations and was used for the molecular docking calculations. The molecular docking results suggested that nevirapine prefers to bind on the minor groove of ct-DNA.  相似文献   

16.
    
In the present work, the mechanism of the interaction between a β1 receptor blocker, metoprolol succinate (MS) and human serum albumin (HSA) under physiological conditions was investigated by spectroscopic techniques, namely fluorescence, Fourier transform infra‐red spectroscopy (FT‐IR), fluorescence lifetime decay and circular dichroism (CD) as well as molecular docking and cyclic voltammetric methods. The fluorescence and lifetime decay results indicated that MS quenched the intrinsic intensity of HSA through a static quenching mechanism. The Stern–Volmer quenching constants and binding constants for the MS–HSA system at 293, 298 and 303 K were obtained from the Stern–Volmer plot. Thermodynamic parameters for the interaction of MS with HSA were evaluated; negative values of entropy change (ΔG°) indicated the spontaneity of the MS and HSA interaction. Thermodynamic parameters such as negative ΔH° and positive ΔS° values revealed that hydrogen bonding and hydrophobic forces played a major role in MS–HSA interaction and stabilized the complex. The binding site for MS in HSA was identified by competitive site probe experiments and molecular docking studies. These results indicated that MS was bound to HSA at Sudlow's site I. The efficiency of energy transfer and the distance between the donor (HSA) and acceptor (MS) was calculated based on the theory of Fosters' resonance energy transfer (FRET). Three‐dimensional fluorescence spectra and CD results revealed that the binding of MS to HSA resulted in an obvious change in the conformation of HSA. Cyclic voltammograms of the MS–HSA system also confirmed the interaction between MS and HSA. Furthermore, the effects of metal ions on the binding of MS to HSA were also studied.  相似文献   

17.
    
Breast cancer is one of the most common cancer with high morbidity and mortality in women. This study aimed to explore the potential mechanism of costunolide inducing MCF-7 cells apoptosis by multi-spectroscopy, molecular docking, and cell experiments. The results manifested that costunolide interacted with calf thymus DNA (ct-DNA) in a spontaneous manner, and the minor groove as the preferential binding mode. Furthermore, costunolide inhibited cell proliferation and colony formation. Hoechst 33258 staining showed that cell apoptosis induced by costunolide might be related to DNA damage. The apoptosis mechanism relied on regulating the protein expression of Bax, Bcl-2, p53, Caspase-3 and the activation of p38MAPK and nuclear factor κB (NF-κB) pathways. This study will provide some experimental basis and potential therapeutic strategy for breast cancer treatment.  相似文献   

18.
    
The binding of benzoyl peroxide (BPO), a flour brightener, with calf thymus DNA (ctDNA) was predicted by molecular simulation, and this were confirmed using multi‐spectroscopic techniques and a chemometrics algorithm. The molecular docking result showed that BPO could insert into the base pairs of ctDNA, and the adenine bases were the preferential binding sites which were validated by the analysis of Fourier transform infrared spectra. The mode of binding of BPO with ctDNA was an intercalation as supported by the results from ctDNA melting and viscosity measurements, iodide quenching effects and competitive binding investigations. The circular dichroism and DNA cleavage assays indicated that BPO induced a conformational change from B‐like DNA structure towards to A‐like form, but did not lead to significant damage in the DNA. The complexation was driven mainly by hydrogen bonds and hydrophobic interactions. Moreover, the ultraviolet–visible (UV–vis) spectroscopic data matrix was resolved by a multivariate curve resolution–alternating least–squares algorithm. The equilibrium concentration profiles for the components (BPO, ctDNA and BPO–ctDNA complex) were extracted from the highly overlapping composite response to quantitatively monitor the BPO–ctDNA interaction. This study has provided insights into the mechanism of the interaction of BPO with ctDNA and potential hazards of the food additive.  相似文献   

19.
    
The interaction of a novel macrocyclic copper(II) complex, ([CuL(ClO4)2] that L is 1,3,6,10,12,15-hexaazatricyclo[13.3.1.16,10]eicosane) with calf thymus DNA (ct-DNA) was investigated by various physicochemical techniques and molecular docking at simulated physiological conditions (pH = 7.4). The absorption spectra of the Cu(II) complex with ct-DNA showed a marked hyperchroism with 10 nm blue shift. The intrinsic binding constant (Kb) was determined as 1.25 × 104 M?1, which is more in keeping with the groove binding with DNA. Furthermore, competitive fluorimetric studies with Hoechst33258 have shown that Cu(II) complex exhibits the ability to displace the ct-DNA-bound Hoechst33258 indicating that it binds to ct-DNA in strong competition with Hoechst33258 for the groove binding. Also, no change in the relative viscosity of ct-DNA and fluorescence intensity of ct-DNA-MB complex in the present of Cu(II) complex is another evidence to groove binding. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the binding reaction. The experimental results were in agreement with the results obtained via molecular docking study.  相似文献   

20.
This work deals with the commonly studied cyclic oligosaccharide and gains importance as it is entered on a drug delivering carbohydrate and provides insight into the oligosaccharide complex–biomolecular interaction. The binding of a flavone, baicalein, to β-cyclodextrin and calf thymus DNA is studied. The binding of baicalein to calf thymus DNA in the presence of β-cyclodextrin is analysed using the UV–vis absorption and fluorescence spectroscopy. The mode of binding and structure of the baicalein–β-cyclodextrin complex are reported. The role of the structure and the stoichiometry of the inclusion complex of baicalein–β-cyclodextrin in its influence on DNA binding are analysed.

Highlights

? This paper deals with the binding of a flavone, baicalein to β-cyclodextrin and/or DNA.

? The inclusion complexation between baicalein and β-cyclodextrin is analysed.

? The stoichiometry and the binding strength of the inclusion complex is reported.

? The role of β-cyclodextrin in tuning the binding of baicalein to DNA is emphasized.

? Spectroscopic and docking analysis are used to articulate the results.  相似文献   

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