Search

Hemoperfusion has become the third-generation treatment strategy for patients suffering from hyperbilirubinemia, but adsorbents used for bilirubin removal mostly face intractable problems, such as unsatisfactory adsorption performance and poor hemocompatibility. Metal–organic frameworks (MOFs) are promising adsorbents for hemoperfusion due to their high specific surface areas and easily modified organic ligands. However, their microporous properties and separation have hampered their application. Here, a novel hierarchical core–shell nanoplatform (named Double-PEG) with tailored binding sites and pore sizes based on Fe3O4@C and Uio66-NH2 was constructed. Notably, Double-PEG showed excellent bilirubin uptake of up to 1738.30 mg g−1 and maintained excellent bilirubin removal efficiency in simulated biological solutions. A study on the adsorption mechanism showed that the adsorption of Double-PEG towards bilirubin tended to be chemical adsorption and in accordance with the Langmuir model. Besides, the good separability, recyclability, cytotoxicity and hemocompatibility of Double-PEG show great potential in hemoperfusion therapy. The finding of this study may provide a novel insight into the application of MOF materials in the field of hemoperfusion.

HER2+ breast cancer is highly aggressive and proliferative even after multiple chemotherapy regimens. At present, the available clinical treatment duration of chemotherapeutic agents is limited by severe toxicity to noncancerous tissues, which are attributed to insufficient targeting. Here, we designed an active-targeted and pH-responsive liposome to improve the treatment. The ideas were as follows: (1) using liposome as a nano-delivery system for HER2 inhibitor (lapatinib; LAP) to reduce the toxicity; (2) modifying the capsule with T7 peptide for specific targeted delivery to the tumor cells, and (3) enabling the capsule with the pH-sensitive ability and triggering sustained drug release at extracellular weakly acidic microenvironment to emerge toxicity in tumors and to improve curative effects. It was found that T7 peptide-modified pH-sensitive liposome (T7-LP) was more effective and safer than free drug and unmodified liposome, and reduced drug-induced side effects and noncancerous toxicity. These results support the application potential of T7-LP in improving the efficacy of LAP in HER2+ breast cancer treatment. It might be a novel LAP formulation as a clinical agent.

Ertugliflozin is a potent and selective inhibitor of sodium-dependent glucose cotransporters 2 (SGLT2) and used as a monotherapy to improve glycemic control in adult patients with type 2 diabetes. In this study, ertugliflozin binding to human serum albumin (HSA) was investigated by multispectroscopic and computer simulations. The fluorescence spectra demonstrated that the quenching mechanism of ertugliflozin and HSA was static quenching. Thermodynamic parameters indicated that hydrogen bonding and van der Waals forces played a key role in the binding. Fluorescence competition experiments and molecular docking revealed that ertugliflozin bound to HSA sites II. In three-dimensional fluorescence, circular dichroism spectroscopy, and molecular dynamics simulation, ertugliflozin did not affect the basic skeleton structure of HSA but slightly increased the α-helical structure content and changed the microenvironment around amino acid residues. Results provide valuable information on the basis of the interaction of ertugliflozin with HSA.

Combination therapy including anticancer drugs usually induces synergistic effects, especially in combination with natural compounds as a chemical sensitizer. Nano-based drug delivery technology is also effective in solving the toxicity of single drugs at high doses. In this study, we established a co-delivery strategy for abemaciclib (ABE) combined with vitamin E succinate (VES) based on HA-modified calcium phosphate (CaP) nanomaterials to enhance anti-cancer effect. The nano-sized HA/CaP particles (90 nm) have a hollow structure. Surprisingly, after modification with HA, HA/CaP has more pH sensitivity. CaP released 30% ABE and 91% VES at pH 7.4, whereas HA/CaP vsreleased 14% ABE and 32% VES at the same pH. Cell experiments showed that HA/CaP/ABE-VES had stronger cell inhibitory effect on MCF-7 compared with CaP/ABE-VES. This inorganic/organic composite for the co-delivery of ABE and VES has obvious tumor inhibition effect, and is ideal for anti-tumor drug delivery.

Methyl ferulate (MF) is an alkyl ferulate ester that widely exists in edible plants and has application value in the food and medicine industries. Thus, its effect on biological macromolecules should be considered. In this study, we exploit saturation transfer difference NMR (STD-NMR) to characterize the interaction of all protons of MF with human serum albumin (HSA) at the molecular level. STD-NMR and Ka (1.298 × 103 M−1) revealed that protons H1–6 and H8 bound to HSA with a medium affinity. Binding epitope mapping further showed that the aromatic ring played a key role in the HSA–MF interaction. STD-NMR site-marker-displacement experiments and circular dichroism spectroscopy revealed that MF prefered to bind to site II of HSA without changing the basic skeleton of HSA. Computer simulations confirmed these experimental results. Overall, this work elucidates the molecular level interaction of MF with HSA and provides new insights into the possibility of the potential applications of MF in the food and medicine industries.

Dabrafenib is a novel targeted antimelanoma drug. The present work explored the binding mechanism of dabrafenib-human serum albumin (HSA) and the effect on the esterase-like activity and antioxidant activity of HSA by using 19F NMR, spectroscopy methods, and molecular dynamics simulation. The results of 19F NMR, fluorescence, and time-resolved fluorescence spectroscopy revealed that dabrafenib spontaneously binds to the subdomain IIIA of the HSA by hydrophobic action and forms a static complex. The binding affects the esterase-like activity of HSA but not its antioxidant activity. According to the results of molecular dynamics simulation, dabrafenib interacts with Arg410 and Tyr411, which are the key residue associated with the esterase-like activity of HSA. Meanwhile, dabrafenib does not interact with Cys34, the key residue associated with the antioxidant activity of HSA. The results of circular dichroism spectroscopy and molecular dynamics simulation show that the conformation of HSA is not affected by the binding of dabrafenib. This study can provide useful information for understanding the pharmacokinetic properties of dabrafenib.

This study aimed to develop a novel sustained release system for mesalazine (MSZ) by preparing hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex loaded chitosan (CS) nanoparticles (NPs). The HP-β-CD/MSZ complex was prepared at 1:1 stoichiometry and characterized by using various analysis techniques. The HP-β-CD/MSZ/CS NPs prepared under the optimum condition had a spherical shape (90±17 nm diameter), a narrow size distribution, and a high loading efficiency. Compared with free MSZ, the HP-β-CD/MSZ/CS NPs exhibited an obvious sustained release of MSZ. The activity of the NPs against a cytokine-triggered inflammatory response was evaluated in cytokine-stimulated HT-29 cell lines by monitoring key inflammatory mediators. The results revealed that compared with free MSZ, the NPs more strongly inhibited the production of NO, PGE2, and IL-8, indicating the NPs possibly had better anti-inflammatory effects. Therefore, the established HP-β-CD/MSZ/CS NPs may be a promising delivery system of MSZ.

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 × 10

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.

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.

Telaprevir (TVR) is a first-generation protein inhibitor approved in 2011 for the treatment of chronic hepatitis C, a global epidemic that threatens the human health. This study investigated the interaction between TVR and human serum albumin (HSA) by combining spectroscopic methods and molecular modeling. Fluorescence experiments indicated that TVR could bind to HSA through a static process with a moderate affinity, and the static mechanism was confirmed by time-resolved fluorescence spectroscopy. Negative free energy change obtained from thermodynamic parameters suggested a spontaneous binding reaction between TVR and HSA. Hydrogen bonds and van der Waals force were found to play major roles in the binding process, according to the negative enthalpy and entropy changes. Molecular dynamics (MD) simulation further verified the driving forces, and indicated that hydrophobic force and electrostatic interactions were also involved in the binding. The site I binding mode was demonstrated by site marker displacement experiments and MD simulations. The TVR–HSA complex was stabilized after 30 ns with a binding energy of about −298.4 KJ mol−1, and a less compacted HSA was induced by binding with TVR. Moreover, binding with TVR caused microenvironmental and conformational changes in HSA, based on their synchronous fluorescence, three-dimensional fluorescence, and circular dichroism spectra.

In this study, a new reasonable interpretation of azilsartan form II was suggested which had been reported as a 1,4-dioxane solvate in the literature. Multiple evidence has indicated that azilsartan form II obtained in this study was not a 1,4-dioxane solvate. Results of single crystal diffraction showed that the chemical formula of azilsartan form II was C25H20N4O5•1.25H2O. The apparent solubility and intrinsic dissolution rate of azilsartan form II were greater than that of form I in pH 6.8 phosphate buffer solution at 37 °C. Results of dynamic vapour sorption indicated that azilsartan form I was hardly hygroscopic. Results of accelerated stability test showed that azilsartan form I and II remained stable after 6 months of storage. Differential scanning calorimetry results showed that azilsartan form II had a lower melting point than form I. A cleaner and more efficient preparation method for azilsartan form II was provided. Azilsartan form II could be prepared through the liquid-assisted grinding method by using a very small amount of tetrahydrofuran (η = 0.2 μL mg−1) or acetone (η = 0.3 μL mg−1). Azilsartan form II presents an alternative solid form for pharmaceutical preparation.

Ligand-receptor molecular recognitionis the basis of biological process. The Saturation Transfer Difference-NMR (STD-NMR) technique has been recently used to gain qualitative and quantitative information about physiological interactions at atomic-resolution. The molecular recognition patterns between Vitamin B12 (VB12) and human serum albumin (HSA) were investigated by STD-NMR supplemented by other spectroscopies and molecular docking. STD-NMR delivered a complete picture that the substituent groups on the tetrapyrrole ring of VB12 interacted with site III of HSA through binding epitope mapping and competitive probe experiments. STD-NMR and fluorescence results proved the moderate binding capability of VB12 and clarified a static, spontaneous, and temperature-sensitive binding mechanism. 3D-fluorencence, FT-IR and circular dichroism spectra showed a compact protein structure by interacting with VB12. Size distribution and surface hydrophobicity showed the surface properties changes of HSA caused by the binding of VB12. Computer simulation confirmed the recognition mode in theory and was compared with experiments. This work is beneficial for understanding the safety and biological action of VB12, and will attract researchers interested in NMR technology.

Empagliflozin is an oral sodium glucose co-transporter-2 inhibitor for type 2 diabetes mellitus. The interaction between empagliflozin and human serum albumin (HSA) was investigated experimentally and theoretically. Fluorescence quenching and time-resolved fluorescence spectroscopy indicated that the quenching mechanism of empagliflozin and HSA was dynamic and that the effective binding constant at body temperature was 3.495 × 10

Nanoscale metal-organic frameworks (NMOFs) have attracted considerable attention for controlled drug delivery. However, the interaction between nanoparticles and the biological macromolecules of physiological system must be valued because the formed protein corona will endow NMOFs with new biorecognition properties. In this study, we carried out detailed protein adsorption studies in vitro and cell uptake tests of HeLa cells for nanospherical Uio66 and nanooctahedral Uio67. Uio67 with higher binding constants to human serum albumin needed to combine more protein molecules to achieve colloidal stability state than that needed by Uio66, and this phenomenon led Uio67 to aggregate under the same incubation condition due to the formation of a single-layer protein. Uio67 also induced an evident conformation change in protein to stabilize the combination. In particular, the cell uptake efficiencies of the two systems showed a significant thickness dependence on the protein corona. When samples incubated in 10% fetal bovine serum (FBS), the intracellular rate was the highest for both systems, but the rate was not proportional to the FBS concentration. Results of this work are important to the development of the considerable potential NMOFs-based medicals and also provide additional insight into protein corona.

In this study, a novel Bruton’s tyrosine kinase inhibitor, ibrutinib, was loaded into chitosan/sulfobutylether-β-cyclodextrin nanoparticles (NPs). NPs have gained high loading efficiency for the hydrophobic drug due to the inclusion of cyclodextrin. Ibrutinib-loaded NPs with an average diameter of 277.9 nm and ζ-potential of +19.1 mV were obtained after regulating several influencing factors. Electrostatic reaction between mucin and NPs indicated that the NPs had a mucoadhesive property. Kinase catalytic phosphorylation was monitored by capillary zone electrophoresis and found that chitosan/sulfobutylether-β-cyclodextrin NPs did not weaken ibrutinib activity on the target kinase. In vitro drug release studies revealed that ibrutinib-loaded NPs exhibited a significantly slower gastric-release rate. This study applied a feasible nanocarrier for ibrutinib delivery, and the potential nanoformulation maintains drug activity and shows a sustained release property. These outcomes are helpful for the formulation exploitation of tyrosine kinase inhibitors.

Introduction of hydrophilic groups can improve the solubility of leading drugs but inevitably affect their interaction with proteins. This study selected sirtuin inhibitors Tenovin-1 (T1) and Tenovin-6 (T6) as drug models to determine differences in binding mode to human serum albumin (HSA). T1 and T6 quenched the endogenous fluorescence of HSA via static quenching mechanism. Introduction of hydrophilic groups greatly reduced the binding constant, i.e., from 1.302 × 104 L mol−1 for the HSA-T6 system to 0.128 × 104 L mol−1 for the HSA-T1 system. HSA-T1 system was mainly driven by electrostatic interactions while that of HSA-T6 system was hydrophobic interaction and both systems were spontaneous reactions. Site marker experiments and molecular docking indicated that both systems mainly bound to the hydrophobic site I of HSA. Molecular dynamics (MD) simulation analysis further revealed that Tyr148, Tyr150 and Arg257 residues played a key role in this recognition process for both systems. In particular, T6 maintained additional several hydrogen bonds with the surrounding residues. T1 had almost no effect on the esterase-like activity of HSA, but T6 inhibited the hydrolysis of p-NPA. Furthermore, differential scanning calorimetry (VP-DSC), circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy confirmed that HSA in the T6 system undergone a more significant conformational transition than that in the T1 system.

Tonalide (AHTN) is a new category of pollutants with a wide range of potential environmental and organismal hazards due to its persistence and lipophilicity, and the safety evaluation of this pollutant under physiological condition is a pressing issue. This study investigated the mechanism of interaction between AHTN and human serum albumin (HSA) that is an important transporter in plasma using multiple spectroscopic, molecular docking, and dynamics simulation methods. The steady-state fluorescence and fluorescence lifetime experiments showed that AHTN quenches the inherent fluorescence of HSA through a static quenching mechanism. Thermodynamic parameters exhibited that the binding constant of AHTN and HSA is of the order of 10^4 L/mol, and the binding is a spontaneous process of moderate strength with hydrophobic forces as the main driving force. Site competition revealed that AHTN binds to site I of HSA IIA subdomain, which was evidenced by the molecular docking results. AHTN altered the HSA amino acid microenvironment and conformation can be derived from three-dimensional fluorescence, circular dichroism spectroscopy, and molecular dynamics simulation. The computer simulations corroborate the experimental results positively. Moreover, AHTN acted as a competitive inhibitor to weaken the esterase-like activity of HSA, leading to impaired function of HSA. Results suggest that interactions between AHTN and HSA may affect the normal structure and activities of the protein, this insight will be helpful to provide some basic information to further explore the potential hazards of AHTN in humans.

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.

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 Sudlow's 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.

Electromechanical changes in type I collagen caused by diseases are pivotal for monitoring bone health and offering informative message of constructing biobased smart devices. Here, we employ a mouse model of osteogenesis imperfecta (oim/oim), which is genetically modified through mutating the α-2 chain to α-1 chain in the collagen fibrils of the wild-type model (+/+ or heterotrimer), resulting in three α-1 chains in the collagen fibrils (i.e., homotrimer). Piezoresponse force microscopy (PFM) is used to directly visualize the sub-micrometer structures and piezoresponses of +/+ and oim/oim collagen fibers. Results show that the compact and highly ordered +/+ collagen fibers possess larger in-plane piezoresponses than the loosely packed and randomly distributed oim/oim collagen fibers. The mean values of the lateral PFM amplitude are 108.53 pm and 77.72 pm with interquartile ranges of 98.56–117.47 pm and 71.21–85.93 pm for +/+ and oim/oim collagen fibers, respectively. Molecular simulations demonstrate that the structural stability and electrically induced activity of heterotrimer are better than those of homotrimer, suggesting better biopiezoelectricity of comprising diverse polar residues (atomic charges) within the oriented heterotrimeric collagen molecular structure. Our study provides a new insight into the functional changes of human osteogenesis imperfecta.

Drug polymer carriers usually have good sustained release character. In this study, epichlorohydrin was used as cross-linking agent for synthesizing the beta-cyclodextrin polymer microspheres (β-CDPM) by adopting the method of inverse emulsion polymerization. The scanning electron microscope, infrared spectra, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric, 1H NMR and solid state nuclear magnetic resonance were utilized to characterize the structure, surface morphology, thermal stability and crystallinity of the obtained β-CDPM. In vitro release experiment of ornidazole-β-CDPM under preferred experimental condition was studied and the cumulative release curves at different pH values were obtained. The drug loading rate of β-CDPM is 8.86% under preferred process. The release time of the synthesized microspheres was 9 h, which showed good sustained-release behavior. Antibacterial test result indicated that β-CDPM did not affect the antibacterial activity of ornidazole.

The binding properties between γ-lactone essences and HSA were investigated to explore interactional mechanism and influence of ligand side chains on binding via computer simulations, microscopy, and multiple-spectroscopies. Docking and molecular dynamics presented protein recognition mode with low fluctuations. NMR analysis revealed that the lactone ring of ligands was the main group bound to HSA. UV–vis and lifetime results revealed that the combination was static quenching mechanism with binding constants of 102–103 L/mol. FTIR and CD spectra showed conformational changes in the protein secondary structure induced by ligands. Side chains affect the binding process through steric hindrance and hydrophobicity. AFM images showed the four compounds caused different effects on molecular size of HSA. In conclusion, the binding ability and the protein secondary structure changes had a positive correlation with the length of side chain. These studies are beneficial for understanding the safety and biological action of γ-lactone essences.

Interaction between ulipristal acetate (UPA) and human serum albumin (HSA) was investigated in simulated physiological environment using multi-spectroscopic and computational methods. Fluorescence experiments showed that the quenching mechanism was static quenching, which was confirmed by the time-resolved fluorescence. Binding constants (

The interaction mechanism between olaparib (OLA) and human serum albumin (HSA) has been investigated using experimental and computational techniques. An NMR relaxation approach based on the analysis of proton selective and non-selective spin–lattice relaxation rates at different temperatures can provide quantitative information about the affinity index and the thermodynamic equilibrium constant of the OLA–HSA system. The affinity index and the thermodynamic equilibrium constant decreased as temperature increased, indicating that the interactions between OLA and HSA could be weakened as temperature increased. Molecular docking and dynamics simulations revealed that OLA stably bound to subdomain II (site 1), and OLA could induce the conformational and micro-environmental changes in HSA. CD results suggested that α-helix content decreased after OLA was added, demonstrating that OLA affected the secondary structure of HSA.

Sitafloxacin (STFX) is a new generation of broad-spectrum oral fluoroquinolones. STFX has significantly enhanced antibacterial activity than most similar drugs. Clinically, this drug is mainly used to treat respiratory and urinary tract infections and other serious bacterial infections. In this study, the interaction between sitafloxacin and human serum albumin (HSA) was investigated by spectroscopic methods and molecular simulations. Fluorescence quenching experiments showed that the interaction mechanism between STFX and HSA was static quenching, which was confirmed by time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrophobic and electrostatic forces played a key role in this mechanism. Probe experiments and molecular docking results indicated that the major binding of STFX was at site I. 3D fluorescence showed that the insertion of STFX had minimal impact on the microenvironment. Analysis of the protein secondary structure showed that the insertion of STFX had little effect on the secondary structure of the protein. Hydrophobicity experiments showed the slight decrease in the overall hydrophobicity index of the system. Molecular dynamics simulations further validated the stability of the HSA-STFX complex. This study are useful for further drug development, in vivo toxicity studies, and can provide guidance for the clinical application of STFX to study its pharmacokinetic properties.

The interactions between 2-{4-[(3S)-piperidin-3-yl] phenyl}-2H-indazole-7-carboxamide (niraparib) and human serum albumin (HSA) were investigated through fluorescence and computational studies. Fluorescence experiments showed that the static quenching mechanism and the binding constant of the HSA–niraparib system at a single binding site was approximately 4 × 104 L mol−1. Thermodynamic constants indicated that the binding of niraparib to HSA was mainly driven by electrostatic interactions. Competition experiments and molecular docking simulations revealed that niraparib bound to site III of HSA. Synchronous fluorescence and Fourier transform infrared spectroscopy (FT-IR) results suggested that interactions between niraparib and HSA could affect the conformation and microenvironment of HSA. Circular dichroism (CD) measurements revealed that the α-helix contents of HSA negligibly increased after binding with niraparib. Molecular dynamics simulations demonstrated the stability of the binary HSA–niraparib system and confirmed that electrostatic forces accounted for the dominant contribution to system energy between HSA and niraparib.

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.

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.

Tertiary butylhydroquinone (TBHQ) is a water-insoluble antioxidant. In this study, three cyclodextrin inclusion complexes were prepared to improve the water solubility of TBHQ and expand its range of application. Analysis of phase solubility indicated that TBHQ can form 1:1 inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and dimethyl-beta-cyclodextrin (DM-β-CD) and 1:2 inclusion complex with beta-cyclodextrin (β-CD). The possible inclusion configuration between TBHQ and CDs was determined through FT-IR, PXRD, DSC, NMR, and SEM analyses. Results were validated by theoretical study of AutoDock molecular docking. The scavenging effects of the inclusion complexes were not effective on DPPH radical but higher on hydroxyl, superoxide and ABTS+ radicals than that of TBHQ monomer. Moreover, the water solubility of TBHQ increased after complexation with HP-β-CD and DM-β-CD. The stability of TBHQ is related to the type of storage materials used, and the stability can be improved by complexation with CDs.

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.

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 105 l/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.

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.

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.