Gongke Wang

Molecular mechanism of interaction between norfloxacin and trypsin studied by molecular spectroscopy and modeling

The molecular mechanism of the binding of norfloxacin (NRF) to trypsin was investigated by fluorescence, synchronous fluorescence and UV-vis absorbance spectroscopy and molecular modeling at physiological conditions. The quenching mechanism and the binding mode were investigated in terms of the association constants and basic thermodynamic parameters. The results of spectroscopic measurements suggested that NRF have a strong ability to quench the intrinsic fluorescence of trypsin through static quenching procedure. Moreover, fluorescence experiments were also performed at different values of pH to elucidate the effect of pH on the binding. The NRF-trypsin complex was stabilized by hydrophobic forces and hydrogen bonding, via tryptophan residue as indicated from the thermodynamic parameters, which was consistent with the results of molecular docking and accessible surface area calculations.

Study of interaction between human serum albumin and three antioxidants: ascorbic acid, α-tocopherol, and proanthocyanidins.

Ascorbic acid, α-tocopherol and proanthocyanidins are three classic dietary antioxidants. In this study, the interaction between the three antioxidants and human serum albumin (HSA) was investigated by several spectroscopic techniques. Experimental results proved that the three antioxidants quench the fluorescence of HSA through a static (proanthocyanidins) or static-dynamic combined quenching mechanism (ascorbic acid and α-tocopherol). Thermodynamic investigations revealed that the combination between ascorbic acid or proanthocyanidins and HSA was driven mainly by electrostatic interaction, and the hydrophobic interactions play a major role for α-tocopherol-HSA association. Binding site I was found to be the primary binding site for ascorbic acid and proanthocyanidins, and site II for α-tocopherol. Additionally, the three antioxidants may induce conformational and microenvironmental changes of HSA.

Exploring the binding mechanism of dihydropyrimidinones to human serum albumin: Spectroscopic and molecular modeling techniques

The binding mechanism of molecular interaction between 5-(ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (a dihydropyrimidinones derivative, EMPD) and human serum albumin (HSA) was studied using spectroscopic methods and modeling technique. The quenching mechanism was investigated in terms of the binding constants and the basic thermodynamic parameters. The results of spectroscopic measurements suggested that EMPD have a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. The drug-protein complex was stabilized by hydrophobic forces and hydrogen bonding as indicated from the thermodynamic parameters and synchronous fluorescence spectra, which was consistent with the results of molecular docking and accessible surface area calculation. Competitive experiments indicated that a displacement of warfarin by EMPD, which revealed that the binding site of EMPD to HSA was located at the subdomains IIA. The distance between the donor and the acceptor was 4.85nm as estimated according to Försters theory of non-radiation energy transfer. The effect of metal ions on the binding constants was also investigated. The results indicated that the binding constants between EMPD and HSA increased in the presence of common metal ions.

Study on the Interaction of an Anthracycline Disaccharide with DNA by Spectroscopic Techniques and Molecular Modeling

This study was designed to examine the interaction of 4′-O-(a-L-Cladinosyl) daunorubicin (DNR–D5), a disaccharide anthracycline with calf thymus deoxyribonucleic acid (ctDNA) by UV/Vis in combination with fluorescence spectroscopy and molecular modeling techniques under physiological conditions (Britton–Robinson buffer solutions, pH = 7.4). By the analysis of UV/Vis spectrum, it was observed that upon binding to ctDNA the anthraquinone chromophore of DNR–D5 could slide into the base pairs. Moreover, the large binding constant indicated DNR–D5 had a high affinity with ctDNA. At the same time, fluorescence spectra suggested that the quenching mechanism of the interaction of DNR–D5 to ctDNA was a static quenching type. The binding constants between DNR–D5 and ctDNA were calculated based on fluorescence quenching data at different temperatures. The negative ∆G implied that the binding process was spontaneous, and negative ∆H and negative ΔS suggested that hydrogen bonding force most likely played a major role in the binding of DNR–D5 to ctDNA. Moreover, the results obtained from molecular docking corroborate the experimental results obtained from spectroscopic investigations.

β-Carotene and astaxanthin with human and bovine serum albumins

β-Carotene and astaxanthin are two carotenoids with powerful antioxidant properties. In this study, the interaction of these two carotenoids with human serum albumin (HSA) and bovine serum albumin (BSA) under physiological conditions was investigated using several spectroscopic techniques. The experimental results indicate the quenching mechanism of HSA/BSA, by the two carotenoids, is a static process. The binding constants and number of binding sites were evaluated at different temperatures. Thermodynamic investigations revealed the interaction between the two carotenoids and HSA/BSA is synergistically driven by enthalpy and entropy, and hydrophobic forces and electrostatic attraction have a significant role in the reactions. Binding site I was found to be the primary binding site for β-carotene and astaxanthin. In addition, as shown by synchronous fluorescence spectroscopy and FT-IR, the two carotenoids may induce conformational and micro-environmental changes in HSA/BSA.

Interaction of procyanidin B3 with bovine serum albumin

Proanthocyanidins are a mixture of monomers, oligomers, and polymers of flavan-3-ols that are widely distributed in the plant kingdom. One of the most widely studied proanthocyanidins is procyanidin B3. In this study, the interaction between procyanidin B3 and bovine serum albumin (BSA) was investigated using isothermal titration calorimetry (ITC), in combination with fluorescence spectroscopy, UV-vis absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, circular dichroism (CD) spectroscopy and molecular docking. Thermodynamic investigations reveal that the electrostatic interaction and hydrophobic interaction are the major binding forces in the binding of procyanidin B3 to BSA. The binding of procyanidin B3 to BSA is synergistically driven by enthalpy and entropy. Fluorescence experiments suggest that procyanidin B3 can quench the fluorescence of BSA through a static quenching mechanism. The obtained binding constants and the equilibrium fraction of unbound procyanidin B3 show that procyanidin B3 can be stored and transported from the circulatory system to reach its target organ. Binding site I is found to be the primary binding site for procyanidin B3, which is consistent with the result of molecular docking studies. Additionally, as shown by the UV-vis absorption, synchronous fluorescence spectroscopy, FT-IR and CD, procyanidin B3 may induce conformational and microenvironmental changes of BSA.

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.

Probing the binding behavior and kinetics of silver nanoparticles with bovine serum albumin

Nanomaterials have been utilized as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by our limited understanding and control over their interactions with specific biological systems. Elucidating the binding mechanism and kinetic behavior of metal nanomaterials with proteins is significant, and herein we investigate the interaction of a model protein, bovine serum albumin (BSA), with silver nanoparticles (AgNPs) using fluorescence, synchronous fluorescence, ultraviolet (UV) absorption, Fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) techniques in aqueous solutions. The experimental results indicated that the binding of AgNPs to BSA seems to be of a static quenching type with the formation of a ground state complex. With the determination of the binding constants and thermodynamic parameters, it is suggested that the binding process of AgNPs to the surface of BSA is spontaneous. Moreover, it was demonstrated that the main acting forces between the AgNPs and BSA may be hydrophobic and electrostatic interactions. At the same time, synchronous fluorescence, FT-IR and CD techniques were employed to analyze the conformational change of BSA in the presence of AgNPs. The results of kinetic studies reveal that the adsorption of BSA on the AgNP surface tends to have pseudo-second-order kinetic characteristics with an obvious hysteresis effect.