Jianming Liu

Study of interaction between human serum albumin and three phenanthridine derivatives: fluorescence spectroscopy and computational approach.

Over the past decades, phenanthridine derivatives have captured the imagination of many chemists due to their wide applications. In the present work, the interaction between phenanthridine derivatives benzo [4,5]imidazo[1,2-a]thieno[2,3-c]quinoline (BTQ), benzo[4,5]imidazo[1,2-a]furo[2,3-c]quinoline (BFQ), 5,6-dimethylbenzo[4,5]imidazo[1,2-a]furo[2,3-c]quinoline (DFQ) and human serum albumin (HSA) were investigated by molecular modeling techniques and spectroscopic methods. The results of molecular modeling simulations revealed that the phenanthridine derivatives could bind on both site I in HSA. Fluorescence data revealed that the fluorescence quenching of HSA by phenanthridine derivatives were the result of the formation of phenanthridine derivatives-HSA complex, and the binding intensity between three phenanthridine derivatives and HSA was BTQ>BFQ>DFQ. Thermodynamics confirmed that the interaction were entropy driven with predominantly hydrophobic forces. The effects of some biological metal ions and toxic ions on the binding affinity between phenanthridine derivatives and HSA were further examined.

The binding affinity of phthalate plasticizers-protein revealed by spectroscopic techniques and molecular modeling.

Phthalate plasticizers have been subjected to close scrutiny and evidences of their toxicity and other negative environmental impacts have arisen as a result of their use in food in some countries. Once entering human body, plasticizers could affect the conformation of human serum albumin and protein function. The interaction between two phthalate plasticizers and human serum albumin was investigated by multispectroscopic techniques and molecular modeling. The alteration in protein conformational stability was determined by fluorescence quenching data. The thermodynamic parameters indicated that the hydrophobic interactions played a major role in the process. In addition, the alterations of HSA secondary structure in the presence of phthalate plasticizers were investigated. Molecular modeling and displacement experiments showed that phthalate plasticizers situated within subdomain IIA (site I) of HSA. Furthermore, the binding distances for the plasticizers-HSA system were provided by the efficiency of fluorescence resonance energy transfer.

Synthesis of imidazole derivatives and the spectral characterization of the binding properties towards human serum albumin.

Small molecular drugs that can combine with target proteins specifically, and then block relative signal pathway, finally obtain the purpose of treatment. For this reason, the synthesis of novel imidazole derivatives was described and this study explored the details of imidazole derivatives binding to human serum albumin (HSA). The data of steady-state and time-resolved fluorescence showed that the conjugation of imidazole derivatives with HSA yielded quenching by a static mechanism. Meanwhile, the number of binding sites, the binding constants, and the thermodynamic parameters were also measured; the raw data indicated that imidazole derivatives could spontaneously bind with HSA through hydrophobic interactions and hydrogen bonds which agreed well with the results from the molecular modeling study. Competitive binding experiments confirmed the location of binding. Furthermore, alteration of the secondary structure of HSA in the presence of the imidazole derivatives was tested.

Binding of helicid to human serum albumin: a hybrid spectroscopic approach and conformational study.

The interaction between human serum albumin and helicid was studied by steady-state fluorescence, ultraviolet-visible, circular dichroism, Fourier transform infrared techniques and molecular modeling. The binding site numbers, association constants, and corresponding thermodynamic parameters were used to investigate the quenching mechanism. The alternations of protein secondary structure in the presence of helicid were demonstrated using synchronous fluorescence, Fourier transform infrared, circular dichroism and three-dimensional fluorescence spectra. The molecular modeling results revealed that helicid could bind to hydrophobic pocket of HSA with hydrophobic and hydrogen bond force. The binding site of helicid in HSA was ascertained. Moreover, an apparent distance of 3.33 nm between the Trp214 and helicid was obtained via fluorescence resonance energy transfer method.

Evaluation of the binding of perfluorinated compound to pepsin: Spectroscopic analysis and molecular docking.

In this paper, we investigated the binding mode of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) to pepsin using spectroscopies and molecular docking methods. Fluorescence quenching study indicated that their different ability to bind with pepsin. Meanwhile, time-resolved fluorescence measurements established that PFOA and PFNA quenched the fluorescence intensity of pepsin through the mechanism of static quenching. The thermodynamic parameters showed that hydrophobic forces were the main interactions. Furthermore, UV-vis, FTIR, three-dimensional fluorescence and molecular docking result indicated that PFCs impact the conformation of pepsin and PFOA was more toxic than PFNA. The conformational transformation of PFOA/PFNA-pepsin was confirmed through the quantitative analysis of the CD spectra. The present studies offer the theory evidence to analyze environmental safety and biosecurity of PFCs on proteases.

Interaction of human serum albumin with novel imidazole derivatives studied by spectroscopy and molecular docking

This study was a detailed characterization of the interaction of a series of imidazole derivatives with a model transport protein, human serum albumin (HSA). Fluorescence and time-resolved fluorescence results showed the existence of a static quenching mode for the HSA-imidazole derivative interaction. The binding constant at 296 K was in the order of 10(4) M(-1), showing high affinity between the imidazole derivatives and HSA. A site marker competition study combined with molecular docking revealed that the imidazole derivatives bound to subdomain IIA of HSA (Sudlows site I). Furthermore, the results of synchronous, 3D, Fourier transform infrared, circular dichroism and UV-vis spectroscopy demonstrated that the secondary structure of HSA was altered in the presence of the imidazole derivatives. The specific binding distance, r, between the donor and acceptor was obtained according to fluorescence resonance energy transfer.

Aflatoxin B1 and aflatoxin M1 induced cytotoxicity and DNA damage in differentiated and undifferentiated Caco-2 cells.

Aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) are natural mycotoxins that frequently present in food and feed and pose risks to human health. There are few data in the literature regarding the impairment of them in the intestine. Therefore, the present study investigated their cytotoxic effect on Caco-2 cells, especially the differentiated ones that resemble mature small intestinal enterocytes. Both undifferentiated (UC) and differentiated (DC) cells were treated with AFB1 and AFM1 at various concentrations for up to 72 h. Cell viability, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production and DNA damage were determined. Data showed that AFB1 and AFM1 significantly inhibited UC and DC cell growth, increased LDH and caused genetic damage in a time- and dose-dependent manner (p < 0.05). In comparison, AFB1 was found to be more toxic than AFM1 on both UC and DC. All these cytotoxic outcomes might be associated with intracellular ROS generation, leading to membrane damage and DNA strand break. Additionally, DC was found to be more sensitive to aflatoxins, which might be due to the alteration of enzymes during cell differentiation. The present study provided the first in vitro evidence of DNA damage of DC induced by AFB1 and AFM1.

The investigation of the binding behavior between ethyl maltol and human serum albumin by multi-spectroscopic methods and molecular docking

This paper was designed to investigate the interaction of ethyl maltol with human serum albumin (HSA) under physiological condition by fluorescence, synchronous fluorescence, three-dimensional fluorescence, Fourier transformation infrared spectra, and molecular docking method. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of HSA by ethyl maltol was static quenching mechanism. The binding constants of ethyl maltol-HSA complexes were observed to be 2.59, 1.88, 1.54, 1.13×10(4) M(-1) at 289, 296, 303 and 310 K, respectively. The thermodynamic parameters, ΔH(0) and ΔS(0) were calculated to be -28.61 kJ mol(-1) and -14.59 J mol(-1) K(-1). Energy transfer from tryptophan to ethyl maltol occurred by a FRET mechanism, and the donor-acceptor distance (3.04 nm) had been determined according to Försters theory. Molecular docking studies revealed that ethyl maltol situated within subdomain IIA (site I) of HSA. Fluorescence displacement experiments also proved the binding sites between ethyl maltol and HSA.

Synthesis and interaction studies of benzimidazole derivative with human serum albumin.

A benzimidazole derivative, 1-(2-picolyl)-3-(2-picolyl) benzimidazole iodide (PPB), was synthesized. Fourier transform infrared spectroscopy (FT-IR), UV-visible, three-dimensional (3D) fluorescence, synchronous fluorescence (SF) and fluorescence spectroscopic methods were used to determine the PPB binding mode and the effects of PPB on protein stability and secondary structure. Fluorescence results revealed the presence of static type of quenching mechanism in the binding of PPB to human serum albumin (HSA). The binding constants between PPB and HSA were obtained according to Scatchard equation. The number of binding sites, the binding constants and the thermodynamic parameters were measured. The results showed a spontaneous binding of PPB to HSA through hydrogen bonds and van der Waals forces. In addition, the distance between PPB and the Trp 214 was estimated via employing the Försters non-radiative energy transfer theory, and was found to be 3.49 nm, which indicated that PPB can bind to HSA with high probability. Site marker competitive experiments indicated that the binding of PPB to HSA primarily took place in subdomain IIA.

Probing the binding properties of dicyandiamide with pepsin by spectroscopy and docking methods

Dicyandiamide (DCD), considered to be a nitrification inhibitor, poses threat to humans health with exposure from milk, infant formula and other food products. In this work, DCD was investigated for its binding reaction with pepsin using spectroscopy and docking methods. Fluorescence experiments indicated DCD quenched the fluorescence of pepsin through a static process. Thermodynamic analysis of the binding data (ΔH0xa0=xa0-21.72xa0kJxa0mol-1 and ΔS0xa0=xa017.61xa0Jxa0mol-1 K-1) suggested the involvement of hydrophobic and hydrogen bonding in the complex formation. The pepsin interacted with DCD at a hydrophobic cavity, leading to a conformational changes in the pepsin, as revealed from UV-vis absorption, Fourier transform infrared, the time-resolved fluorescence, three-dimensional fluorescence and circular dichroism spectral results.