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Binding interaction of a novel fluorophore with serum albumins: steady state fluorescence perturbation and molecular modeling analysis.

Pal U, Pramanik SK, Bhattacharya B, Banerji B, Maiti NC - Springerplus (2015)

Bottom Line: The fluorescence yield of the compound substantially increased inside hydrophobic protein surface and ~30 nm decrease in Stokes' shift, compared to aqueous solution, was observed.Thus, the molecule appears as a new fluorescence probe to report the nature of its binding site in terms of increased fluorescence quantum yield and decreased Stokes' shift.Further it could be useful to detect and study the drug binding site of specific protein of interest.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology (IICB), Kolkata, West Bengal India.

ABSTRACT
Fluorescence emission and anisotropy are widely used to measure the binding parameters and kinetic behavior of reactions that cause a change in the rotational time of a fluorescent molecule. We report here fluorescence emission and anisotropy behavior of a newly synthesized novel naphthalene base fluorophore (methyl 3-[(6-{[2-(tert-butoxy)-2-oxoethyl] (4-methoxyphenyl)amino}naphthalen-2-yl)formamido]propanoate) in several solution conditions including its binding to human and bovine serum albumin proteins both in their native and denatured states. The fluorescence yield of the compound substantially increased inside hydrophobic protein surface and ~30 nm decrease in Stokes' shift, compared to aqueous solution, was observed. Shift in fluorescence excitation peak position from the absorption peak of the molecule was ~8 nm in protein solution. This indicated possible alteration of excited state geometry of the compound by the globular fold of albumins. In addition, we measured the steady state fluorescence anisotropy of the molecule to evaluate several thermodynamic parameters and the results suggested the binding was energetically favorable. The measured ΔG° was ~-30 kJ mol(-1) and the derived dissociation constant was ~10(-6) M. The molecular docking analysis further highlighted the nonspecific association of the compound with the proteins and hydrophobic forces may have a significant role in the binding processes. Under the denatured condition of the protein, the compound lost its binding efficacy and reduction in fluorescence intensity was observed. Thus, the molecule appears as a new fluorescence probe to report the nature of its binding site in terms of increased fluorescence quantum yield and decreased Stokes' shift. It can also report the changes in the binding site due to global change in protein structure such as unfolding/misfolding often linked to several human disorder. Further it could be useful to detect and study the drug binding site of specific protein of interest.

No MeSH data available.


Related in: MedlinePlus

Detailed interaction diagram of compound 5 with serum albumins as obtained by molecular docking experiments. Only the residues common in all three lowest energy complexes generated by AutoDock 4.2, AutoDock Vina and SwissDock are shown. a Interacting residues of BSA and the types of interactions with compound 5. b Interacting residues of HSA and the types of interactions with compound 5
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Fig7: Detailed interaction diagram of compound 5 with serum albumins as obtained by molecular docking experiments. Only the residues common in all three lowest energy complexes generated by AutoDock 4.2, AutoDock Vina and SwissDock are shown. a Interacting residues of BSA and the types of interactions with compound 5. b Interacting residues of HSA and the types of interactions with compound 5

Mentions: Detailed interaction diagrams of the protein–ligand complexes showing the interacting residues and the types of interactions obtained by three different docking programs (AutoDock 4.2, AutoDock Vina and SwissDock) are given in Additional file 1 (Figures S7, S8). The consensus of the interacting residues of BSA and HSA with compound 5 are produced from those interacting diagrams depicted in Additional file 1: Figures S7, S8 and is shown in Fig. 7. We have found that Lys114 and His145 of BSA forms H-Bond with compound 5, whereas, Arg458 forms pi-cation interaction. Other important interacting residues of BSA are Arg144, Ser192, Pro110 and Leu189. In case of HSA, it is found that Arg117 and Tyr138 forms H-bond, whereas, Arg186 and Tyr161 forms pi-stacking with compound 5. Other important interacting residues of HSA are Leu115, Phe157, Leu182, Leu185 and Gly189. Fig. 7


Binding interaction of a novel fluorophore with serum albumins: steady state fluorescence perturbation and molecular modeling analysis.

Pal U, Pramanik SK, Bhattacharya B, Banerji B, Maiti NC - Springerplus (2015)

Detailed interaction diagram of compound 5 with serum albumins as obtained by molecular docking experiments. Only the residues common in all three lowest energy complexes generated by AutoDock 4.2, AutoDock Vina and SwissDock are shown. a Interacting residues of BSA and the types of interactions with compound 5. b Interacting residues of HSA and the types of interactions with compound 5
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582037&req=5

Fig7: Detailed interaction diagram of compound 5 with serum albumins as obtained by molecular docking experiments. Only the residues common in all three lowest energy complexes generated by AutoDock 4.2, AutoDock Vina and SwissDock are shown. a Interacting residues of BSA and the types of interactions with compound 5. b Interacting residues of HSA and the types of interactions with compound 5
Mentions: Detailed interaction diagrams of the protein–ligand complexes showing the interacting residues and the types of interactions obtained by three different docking programs (AutoDock 4.2, AutoDock Vina and SwissDock) are given in Additional file 1 (Figures S7, S8). The consensus of the interacting residues of BSA and HSA with compound 5 are produced from those interacting diagrams depicted in Additional file 1: Figures S7, S8 and is shown in Fig. 7. We have found that Lys114 and His145 of BSA forms H-Bond with compound 5, whereas, Arg458 forms pi-cation interaction. Other important interacting residues of BSA are Arg144, Ser192, Pro110 and Leu189. In case of HSA, it is found that Arg117 and Tyr138 forms H-bond, whereas, Arg186 and Tyr161 forms pi-stacking with compound 5. Other important interacting residues of HSA are Leu115, Phe157, Leu182, Leu185 and Gly189. Fig. 7

Bottom Line: The fluorescence yield of the compound substantially increased inside hydrophobic protein surface and ~30 nm decrease in Stokes' shift, compared to aqueous solution, was observed.Thus, the molecule appears as a new fluorescence probe to report the nature of its binding site in terms of increased fluorescence quantum yield and decreased Stokes' shift.Further it could be useful to detect and study the drug binding site of specific protein of interest.

View Article: PubMed Central - PubMed

Affiliation: Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology (IICB), Kolkata, West Bengal India.

ABSTRACT
Fluorescence emission and anisotropy are widely used to measure the binding parameters and kinetic behavior of reactions that cause a change in the rotational time of a fluorescent molecule. We report here fluorescence emission and anisotropy behavior of a newly synthesized novel naphthalene base fluorophore (methyl 3-[(6-{[2-(tert-butoxy)-2-oxoethyl] (4-methoxyphenyl)amino}naphthalen-2-yl)formamido]propanoate) in several solution conditions including its binding to human and bovine serum albumin proteins both in their native and denatured states. The fluorescence yield of the compound substantially increased inside hydrophobic protein surface and ~30 nm decrease in Stokes' shift, compared to aqueous solution, was observed. Shift in fluorescence excitation peak position from the absorption peak of the molecule was ~8 nm in protein solution. This indicated possible alteration of excited state geometry of the compound by the globular fold of albumins. In addition, we measured the steady state fluorescence anisotropy of the molecule to evaluate several thermodynamic parameters and the results suggested the binding was energetically favorable. The measured ΔG° was ~-30 kJ mol(-1) and the derived dissociation constant was ~10(-6) M. The molecular docking analysis further highlighted the nonspecific association of the compound with the proteins and hydrophobic forces may have a significant role in the binding processes. Under the denatured condition of the protein, the compound lost its binding efficacy and reduction in fluorescence intensity was observed. Thus, the molecule appears as a new fluorescence probe to report the nature of its binding site in terms of increased fluorescence quantum yield and decreased Stokes' shift. It can also report the changes in the binding site due to global change in protein structure such as unfolding/misfolding often linked to several human disorder. Further it could be useful to detect and study the drug binding site of specific protein of interest.

No MeSH data available.


Related in: MedlinePlus