Structural studies of bovine, equine, and leporine serum albumin complexes with naproxen

Bujacz, A.; Zieliński, Kamil; Sekula, B.

doi:10.1002/prot.24583

Cited by 138 publications

(120 citation statements)

References 48 publications

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“…The tridimensional crystal structure of BSA was imported from the Protein Data Bank (PDB code 4OR0) [33] into the Molecular Operating Environment software package (MOE ® 2014; Chemical Computing Group, Montreal, QC, Canada) for a prior optimization that involved the deletion of water molecules and hetero atoms and the supplementation of hydrogen atoms. The compound 3 three dimensional structure was sketched by ChemDraw ® Ultra 14.0, and the minimized energy structure and geometries of compound 3 were attained by MOE ® 2014 software.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

et al. 2017

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As part of the research endeavors to combat cancer, a non-symmetric bis-isatin derivative (compound 3) was synthesized and showed a significant anti-proliferative potency. The current study provides a comprehensive characterization of the interaction of compound 3 with the drug-transporting protein bovine serum albumin (BSA) via the use of spectroscopic tools along with molecular docking studies. Fluorescence spectral measurements showed that the BSA intrinsic fluorescence can be significantly quenched by the addition of compound 3 and the formation of a non-fluorescent complex. Further measurements revealed a static type of quenching with Stern-Volmer and Linweaver-Burk constants of 10 5 . The thermodynamic parameters of the binding were calculated to be ∆S • 105.09 ± 5.32 with ∆H • of −0.72 ± 0.71 and negative ∆G • values. In addition, synchronous fluorescence and 3D fluorescence spectroscopy suggested that compound 3 did not induce conformational changes in BSA. Site competition experiments revealed that compound 3 competes with warfarin within the BSA binding domain (Sudlow site I). This was further confirmed by the molecular docking results showing a binding energy of −25.93 kJ/mol for compound 3-BSA. Hence, the observed results in the present study assumed that the compound 3-BSA binding is spontaneous, involving electrostatic forces and hydrogen bonding.

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Section: Molecular Docking Studiesmentioning

confidence: 99%

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

et al. 2017

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“…The crystallographic structure used was that of BSA in complex with naproxen available at the Protein Data Bank (PDB) access code 4OR0 [37]. Simulations were carried out using GOLD 5.2 (Genetic Optimization for Ligand Docking), a software based on a genetic algorithm to explore the ligand conformational space and fitness function GoldScore [38,39].…”

Section: Methodsmentioning

confidence: 99%

Induction of axial chirality in divanillin by interaction with bovine serum albumin

et al. 2017

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Vanillin is a plant secondary metabolite and has numerous beneficial health applications. Divanillin is the homodimer of vanillin and used as a taste enhancer compound and also a promissory anticancer drug. Here, divanillin was synthesized and studied in the context of its interaction with bovine serum albumin (BSA). We found that divanillin acquires axial chirality when complexed with BSA. This chiroptical property was demonstrated by a strong induced circular dichroism (ICD) signal. In agreement with this finding, the association constant between BSA and divanillin (3.3 x 105 mol-1L) was higher compared to its precursor vanillin (7.3 x 104 mol-1L). The ICD signal was used for evaluation of the association constant, demonstration of the reversibility of the interaction and determination of the binding site, revealing that divanillin has preference for Sudlow’s site I in BSA. This property was confirmed by displacement of the fluorescent markers warfarin (site I) and dansyl-L-proline (site II). Molecular docking simulation confirmed the higher affinity of divanillin to site I. The highest scored conformation obtained by docking (dihedral angle 242°) was used for calculation of the circular dichroism spectrum of divanillin using Time-Dependent Density Functional Theory (TDDFT). The theoretical spectrum showed good similarity with the experimental ICD. In summary, we have demonstrated that by interacting with the chiral cavities in BSA, divanillin became a atropos biphenyl, i.e., the free rotation around the single bound that links the aromatic rings was impeded. This phenomenon can be explained considering the interactions of divanillin with amino acid residues in the binding site of the protein. This chiroptical property can be very useful for studying the effects of divanillin in biological systems. Considering the potential pharmacological application of divanillin, these findings will be helpful for researchers interested in the pharmacological properties of this compound.

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“…35,36 Surface representations for the drug binding pockets, i.e., sites I and II, clearly showed the changes in AGEs modified form of BSA ( Figure 5). Based on the observations, it is (R 194, 196, 198, 217, and 409 as Arg-P) and lysine (K 204 and 413 as CEL) residues have been represented as the ball and stick models in magenta color.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 98%

Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin

2015

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The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs.

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Structural studies of bovine, equine, and leporine serum albumin complexes with naproxen

Cited by 138 publications

References 48 publications

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

Synthesis and Biophysical Insights into the Binding of a Potent Anti-Proliferative Non-symmetric Bis-isatin Derivative with Bovine Serum Albumin: Spectroscopic and Molecular Docking Approaches

Induction of axial chirality in divanillin by interaction with bovine serum albumin

Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin

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