Changling Yan

Exploring DNA binding properties and biological activities of dihydropyrimidinones derivatives

The effects of substituent modifications for three dihydropyrimidinones derivatives on DNA binding properties were investigated using viscometry in combination with spectroscopy and isothermal titration calorimetry (ITC). The results indicated that substitution in 4 rd position of benzene ring has significant effects on DNA binding mode, affinity and energetics. Electron-donating substitution was favorable for intercalating into DNA bases and had higher DNA binding affinity. However, electron-withdrawing substitution was preferable to bind to DNA in partial intercalation mode with relatively weak DNA binding affinity. Simultaneously, electron-donating substitution could result in more favorable binding enthalpy relative to electron-donating substitution and the parent compound. Antitumor activities of these analogs over BEL-7402 and PC-12 cells were studied to explore the structure activity relationships (SARs), which suggested that electron-donating substitution in 4 rd position of benzene ring could greatly enhance the antitumor activities. However, electron-withdrawing substitution has little effect on the antitumor activity. The present results favor the development of potential drugs related with dihydropyrimidinones derivatives in the treatment of some diseases.

Exploring the mechanism of interaction between 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one and human serum albumin: Spectroscopic, calorimetric and molecular modeling studies

In this paper, binding interaction of 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-one (EMMD) with human serum albumin (HSA) under physiological conditions was investigated by using spectroscopy, isothermal titration calorimetry (ITC) and molecular modeling techniques. The results of spectroscopic studies suggested that EMMD have a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. ITC investigations indicated that drug-protein complex was stabilized by hydrophobic forces and hydrogen bonds, which was consistent with the results of molecular modeling studies. Competitive experiments indicated the displacement of warfarin by EMMD, which revealed that the binding site of EMMD to HSA was located at subdomain IIA.

Exploring the interaction of silver nanoparticles with lysozyme: Binding behaviors and kinetics

The role of nanoparticle interaction with biomolecules to form a biocorona is the key to nanoparticle behavior and its consequences in the physiological environment. Since the adsorbed biocorona decides the fate of a nanomaterials in vivo, and thus a comprehensive understanding of the dynamic interactions of the proteins with the nanoparticle is imperative. Herein we investigate the interaction of a model protein, lysozyme with silver nanoparticles (AgNPs) using fluorescence, synchronous fluorescence, UV-vis absorption spectrum and circular dichroism (CD) techniques under the physiological conditions. The results indicated that the binding of AgNPs to lysozyme may be a static quenching mechanism. With the analysis of the fluorescence spectral data, the binding constants and the thermodynamic parameters were determined, which suggests that the binding of AgNPs to lysozyme is a spontaneous process. Moreover, it was demonstrated that the main acting forces between AgNPs and lysozyme may be hydrophobic interactions. At the same time, the conformational change of lysozyme induced by AgNPs was investigated with synchronous fluorescence spectroscopy and CD techniques. The results of kinetic studies reveal that the adsorption of lysozyme on AgNPs surface tends to follow pseudo-second-order kinetic characteristic with obvious hysteresis effect.

Exploring the binding mechanism of phosphoramidate derivative with DNA: spectroscopy, calorimetry and modeling.

In this study, one of the amino phosphine ester derivatives α-(3-hydroxy-4-methoxyphenyl)-N-phenyl-α-aminophosphonate (HMPAP) was synthesized, and the molecular interaction of HMPAP with ct-DNA has been investigated by UV-Vis absorption spectra, fluorescence spectra, isothermal titration calorimetry (ITC) and molecular modeling. The binding constant (K(b)) of HMPAP to ct-DNA at different temperatures were calculated from fluorescence spectra. According to the UV-Vis absorption spectra, ethidium bromide displacement studies and ITC experimental results, we can conclude that HMPAP is an intercalator. The molecular modeling results indicated that HMPAP can slide into the G-C rich region of ct-DNA. ITC data showed that ct-DNA/HMPAP binding is enthalpy controlled. Furthermore, the results obtained from molecular modeling corroborated the experimental results obtanied from spectroscopic and ITC investigations.

Probing the binding of trypsin to glutathione-stabilized gold nanoparticles in aqueous solution.

We investigate the interaction of trypsin with glutathione-stabilized Au nanoparticles (NPs) using fluorescence, synchronous fluorescence and ultraviolet (UV) absorption spectroscopy. We find that trypsin binds strongly to the Au NPs with a static quenching mechanism, and that the interaction is characteristic of positive cooperative binding. Furthermore, we determine the binding constants and the thermodynamic parameters, which suggest that the main binding forces between the glutathione-stabilized Au NPs and trypsin are electrostatic interactions and hydrogen bonding. Analysis of UV-vis absorption spectra suggests that aggregation of the Au NPs occurs in the trypsin/Au NPs system, which significantly alters the conformation of the protein.

DNA binding properties and biological evaluation of dihydropyrimidinones derivatives as potential antitumor agents

The binding properties of two medicinally important dihydropyrimidinones derivatives 5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (EMPD) and 5-(Ethoxycarbonyl)-6-methyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (EMCD) with calf-thymus DNA (ctDNA) were investigated by spectroscopy, viscosity, isothermal titration calorimetry (ITC) and molecular modeling techniques. Simultaneously, their biological activities were evaluated with MTT assay method. The binding constants determined with spectroscopic titration and ITC were found to be in the same order of 10(4)M(-1). According to the results of viscosity studies, fluorescence competitive binding experiment and ITC investigations, intercalative binding was evaluated as the dominant binding modes between the two compounds and ctDNA. Furthermore, the results of molecular modeling corroborated those obtained from spectroscopic, viscosimetric and ITC investigations. Evaluation of the antitumor activities of the two derivatives against different tumor cell lines proved that they exhibited significant tumor cell inhibition rate, accordingly blocking DNA transcription and replication. The present results favor the development of potential drugs related with dihydropyrimidinones derivatives in the treatment of some diseases.

Study on the Binding of Fluoride, Bromide and Iodide to Ovalbumin by Using Ion-Selective Electrodes

The interactions of F(-), Br(-) and I(-) with ovalbumin (OVA) were studied in acetate buffers of pH 5.68, at 288.15 K, 298.15 K and 308.15 K, using ion-selective electrodes. The data for the ion-protein systems were treated according to the Klotz equation, and the number of binding sites and the binding constants were determined. It is shown that the binding sites of F(-) on OVA molecule are more than those of Br(-) and I(-), and that the binding sites of F(-), Br(-) and I(-) on OVA molecule decreases with increasing temperature. At the same time, our studies indicate that the binding constants for the interactions of F(-), Br(-) and I(-) with OVA show a same trend: They decrease as temperature increases. These were reasonably interpreted with the structural and thermodynamic factors. The thermodynamic functions (DeltaG(), DeltaH(), DeltaS()) at different temperatures were calculated with thermodynamic equations, and the enthalpy change for the interactions were also determined by isothermal titration calorimetry (ITC) at 298.15 K, which indicate that the interactions of F(-), Br(-) and I(-) with OVA are mainly electrostatic interaction. Simultaneously, there are also partial desolvation of solutes and solvent reorganization effect.

Exploration of interactions between decyl-β-D-glucopyranoside and bovine serum albumin in aqueous solution

The interactions between decyl-β-D-glucopyranoside (DG) and bovine serum albumin (BSA), in aqueous media, were investigated through the use of surface tension, steady-state fluorescence, and UV-vis absorption spectroscopy measurements. With regard to surface tension, experimental results revealed that the critical micelle concentrations (CMC) within the DG solution, in the absence and presence of BSA, were evaluated as 2.0 mM and 2.34 mM, respectively. Furthermore, the average number of bound DG monomers per BSA molecule was 67 at the critical micelle concentration. Fluorescence and UV-vis absorption spectroscopy indicated that DG had the capacity to quench the intrinsic fluorescence via the formation of DG/BSA complexes. Iodine ion quenching studies have suggested that DG molecules may act to displace tryptophan residues (Trp 214) from their hydrophobic cavities to the surfaces of the protein molecules.