Qiaomei Sun

Binding properties of drospirenone with human serum albumin and lysozyme in vitro.

The interaction of drospirenone (DP) with human serum albumin (HSA)/lysozyme (LYZ) was investigated using different optical techniques and molecular models. Results from the emission and time resolved fluorescence studies revealed that HSA/LYZ emission quenching with DP was initiated by static quenching mechanism. The LYZ-DP system was more easily influenced by temperature than the HSA-DP system. Displacement experiments demonstrated that the DP binding site was mainly located in site 1 of HSA. Based on the docking methods, DP was mainly bound in the active site hinge region where Trp-62 and Trp-63 are located. Conformation study showed that DP had different effects on the local conformation of HSA and LYZ molecules.

Probing the binding interaction of human serum albumin with three bioactive constituents of Eriobotrta japonica leaves: Spectroscopic and molecular modeling approaches.

Corosolic acid (CRA), maslinic acid (MA), and tormentic acid (TA) are three kind of bioactive constituents of Eriobotrta japonica leaves. In this study, plasma protein binding model prediction suggested that the binding ability to HSA was CRA>MA>TA. Furthermore, fluorescence spectroscopy confirmed this prediction. The results from emission and time resolved fluorescence studies revealed that the emission quenching of HSA with CRA, MA, and TA were all initiated by static quenching mechanism. From molecular docking results and site marker competitive experimental results it was possible to make good estimates about CRA, MA, and TA mainly bound to subdomain IIA of HSA. 3D fluorescence, FT-IR and CD spectra indicated that the local conformation of HSA molecules was affected by the presence of CRA, MA, and TA, but at different extents.

Interactions of cinnamaldehyde and its metabolite cinnamic acid with human serum albumin and interference of other food additives

Considering the adverse effect of food additives on humans, thorough research of their physiological effects at the molecular level is important. The interactions of cinnamaldehyde (CNMA), a food perfume, and its major metabolite cinnamic acid (CA) with human serum albumin (HSA) were examined by multiple-spectroscopies. NMR analysis revealed CNMA and CA both bound to HSA, and STD-NMR experiments established CNMA and CA primarily interacted with site I and site II of HSA, respectively. The ligands caused strong quenching of HSA fluorescence through a static quenching mechanism, with hydrophobic and electrostatic interaction between CNMA/CA and HSA, respectively. UV-vis absorption and CD results showed ligands induced secondary structure changes of HSA. Binding configurations were proved by docking method. Furthermore, binding constants of CNMA/CA-HSA systems were influenced by the addition of four other food additives. These studies have increased our knowledge regarding the safety and biological action of CNMA and CA.

Analysis of binding properties and interaction of thiabendazole and its metabolite with human serum albumin via multiple spectroscopic methods

Thiabendazole (TBZ), which is oxidized into 5-hydroxythiabendazole (5-OH-TBZ) in vivo, is a commonly used food preservative. Interactions of TBZ and 5-OH-TBZ with human serum albumin (HSA) were comprehensively studied via multiple spectroscopic methods and molecular docking. This study focussed on the mechanistic and structural information on binding of TBZ and 5-OH-TBZ to HSA to evaluate the impact of the food additive on HSA. 1H NMR spectra of the two ligands showed the binding exists. ITC and fluorescence spectroscopy results revealed that TBZ was a stronger ligand, with a binding constant of 105l/mol and formed a more stable complex with HSA than did 5-OH-TBZ via electrostatic interaction. Spectroscopic results (UV-vis, FT-IR, and CD) showed that TBZ and 5-OH-TBZ caused conformational changes in HSA, in which α-helix and β-turn transformed into β-sheet, causing HSA structure to loosen. Docking programs showed that both TBZ and 5-OH-TBZ bound to HSA via IB.

Determination of potential main sites of apixaban binding in human serum albumin by combined spectroscopic and docking investigations

Apixaban (AP, Eliquis®) is a novel pyrazole-based direct factor Xa inhibitor. This oral drug was developed by Bristol-Myers Squibb and Pfizer to treat and prevent thrombotic disorders. The single crystallographic data of AP were obtained with methanol as a solvent and classified as Form N-1. The interaction of AP with human serum albumin (HSA) was investigated via different spectroscopic techniques and molecular modeling. Fluorescence quenching between AP and HSA was observed to be a static process. Complexation by AP was the primary factor influencing decreases in the fluorescence intensity of HSA. AP fluorescence also decreased by approximately 20%. H-bonding and van der Waals forces played major roles in AP–HSA binding. Displacement experiments and molecular docking results demonstrated that the AP-binding site is mainly found in site 1 of HSA. The effect of AP binding on HSA esterase-like activity also confirmed this binding site. Three-dimensional fluorescence and circular dichroism studies showed that AP exerts minimal effects on the local conformation of HSA. This study provides useful information with which to better understand the utilization of AP.

Investigation on the interaction of antibacterial drug moxifloxacin hydrochloride with human serum albumin using multi-spectroscopic approaches, molecular docking and dynamical simulation

The interaction between moxifloxacin hydrochloride (MOXH) and human serum albumin (HSA) was experimentally and simulatively investigated. Fluorescence quenching presented that MOXH bound to HSA via a static process, resulting in the formation of MOXH–HSA complex. This quenching mechanism was further verified by time-resolved fluorescence. Binding constants (Ka) of the complex were found to be 105 L mol−1 according to fluorescence data, and the calculated thermodynamic parameters indicated that hydrogen bonds and van der Waals force played key roles in the binding process. The UV-vis absorption, synchronous fluorescence, three-dimensional fluorescence, and circular dichroism spectra suggested that binding with MOXH induced the conformational changes on HSA; the hydrophobicity around tryptophan residues increased, the α-helix content increased, whereas the β-sheet and turn content of HSA decreased. Displacement experiments demonstrated that MOXH mainly bound to site I of HSA. Molecular docking results supported the active site and showed that the diazabicyclo of MOXH inserted into the hydrophobic pocket of HSA. Molecular dynamics simulation further ascertained that MOXH steadily bound to site I of HSA. In conclusion, hydrogen bonds and VDW force played major roles in stabilizing the MOXH–HSA complex, and hydrophobic force was also involved in the binding process.

Investigating the interaction mechanism of fluorescent whitening agents to human serum albumin using saturation transfer difference-NMR, multi-spectroscopy, and docking studies

In this study, 2,2′-(4,4′-biphenylylenebisvinylene)bisbenzenesulfonicacid (CBS-X) and its disodiumsalt (CBS) were used as model compounds to investigate the interaction mechanism between 4,4′-distyrylbiphenyl based fluorescent whitening agents (DSBP-FWAs) and human serum albumin (HSA) through various techniques, including 1H saturation transfer difference nuclear magnetic resonance (1H STD-NMR), fluorescence studies, UV-vis absorption, Fourier transform infrared (FT-IR) spectroscopy, circular dichroism (CD) spectroscopy, and molecular docking. The 1H STD-NMR analyses indicated that CBS and CBS-X can bind to HSA at the favored Sudlows sites II and I, respectively. Fluorescence emission spectra showed that CBS and CBS-X quenches HSA fluorescence through a dynamic mechanism, and this was further verified by fluorescence lifetime experiments and UV-vis absorption. Moreover, the effective binding constant values of the two compounds at the same temperature decreased in the order CBS > CBS-X. Furthermore, the energy transfer efficiency for CBS and CBS-X were 50.5% and 40.6%, respectively. Thermodynamic analyses indicated that the binding of CBS and CBS-X with HSA are both primarily controlled by hydrophobic forces. FT-IR and CD spectroscopy provided complementary information on the micro-environmental and conformational changes of HSA with the additions of CBS and CBS-X. Molecular docking further confirmed the NMR and spectroscopic results. Overall, the comparative studies on the interaction mechanism of CBS and CBS-X when binding to HSA may provide useful information for evaluating their effects on the human body.

Propyl gallate/cyclodextrin supramolecular complexes with enhanced solubility and radical scavenging capacity

This study prepared and investigated the inclusion complexes of propyl gallate (PG) with beta-cyclodextrin (β-CD) and its water-soluble derivatives dimethyl-beta-cyclodextrin (DM-β-CD), hydroxypropyl-beta-cyclodextrin (HP-β-CD), and sulfobutylether-beta-cyclodextrin (SBE-β-CD). Phase solubility studies indicated that the formed complexes were in 1:1 stoichiometry. FT-IR, PXRD, DSC, 1H-NMR, ROESY-NMR, and SEM analysis results confirmed the formation of the complexes. The NMR results indicated that the aromatic ring of PG was embedded into the CD cavity. The aqueous solubility of PG was markedly improved, and that of the PG/DM-β-CD complex increased by 365.3 times. In addition, the results of the antioxidant activity assay showed that the hydroxyl radical and superoxide radical scavenging capacities of the complexes increased by 3-11 times and 1-6.5 times, respectively, compared with those of PG under the same concentration. Therefore, CD/PG inclusion complexes with improved solubility and radical scavenging capacity can be used as water-soluble antioxidants in the food industry.

Binding modes of environmental endocrine disruptors to human serum albumin: insights from STD-NMR, ITC, spectroscopic and molecular docking studies

Given that bisphenols have an endocrine-disrupting effect on human bodies, thoroughly exposing their potential effects at the molecular level is important. Saturation transfer difference (STD) NMR-based binding studies were performed to investigate the binding potential of two bisphenol representatives, namely, bisphenol B (BPB) and bisphenol E (BPE), toward human serum albumin (HSA). The relative STD (%) suggested that BPB and BPE show similar binding modes and orientations, in which the phenolic rings were spatially close to HSA binding site. ITC analysis results showed that BPB and BPE were bound to HSA with moderately strong binding affinity through electrostatic interactions and hydrogen bonds. The order of binding affinity of HSA for two test bisphenols is as follows: BPE > BPB. The results of fluorescence competitive experiments using 5-dimethylaminonaphthalene-1-sulfonamide and dansylsarcosine as competitors, combined with molecular docking indicated that both bisphenols are prone to attach to the binding site II in HSA. Spectroscopic results (FT-IR, CD, synchronous and 3D fluorescence spectra) showed that BPB/BPE induces different degrees of microenvironmental and conformational changes to HSA.

Binding behavior of trelagliptin and human serum albumin: Molecular docking, dynamical simulation, and multi-spectroscopy

This study aims to investigate the interaction mechanism of a hypoglycemic agent, trelagliptin (TLP), and human serum albumin (HSA) through computer simulation and assisted spectroscopy methods. Computer simulation including molecular docking and molecular dynamics analysis was conducted under physiological conditions. Molecular docking results indicate that TLP bound to HSA at site I, and the binding behavior was mainly governed by hydrophobic force. Competitive experiments further verified the theoretical conclusion from molecular docking. Molecular dynamics simulation revealed that TLP indeed stably bound to site I of HSA in the hydrophobic subdomain IIA. Moreover, TLP presented a certain effect on the structural compactness of HSA. In molecular dynamics simulation, hydrogen bonds appeared, which suggested the reliability and stability of the combination. The binding energy of the stable phase is around -250 kJ/mol. Fluorescence quenching studies and time-resolved fluorescence analysis indicated that the evident fluorescence quenching phenomenon of HSA could be due to TLP binding initiated by static quenching mechanism. The binding constants (Ka) of the complex were found to be around 104 via fluorescence data, and the calculated thermodynamic parameters indicated that hydrophobic force played major role in the binding of TLP to HSA. Synchronous fluorescence and three-dimensional fluorescence results demonstrated that TLP slightly disturbed the microenvironment of amino residues. Circular dichroism spectra showed that TLP affected the secondary structure of HSA. The theoretical and experimental results showed excellent agreement.