Unusual Binding of a Potential Biomarker with Human Serum Albumin

De, Dipanwita; Kaur, Harpreet; Datta, Anindya

doi:10.1002/asia.201201060

Cited by 15 publications

(9 citation statements)

References 59 publications

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“…Fluorescence quenching of intrinsic fluorophores of proteins has been widely used to study the interactions of ligands with proteins. − This method can reveal the accessibility of quenchers to protein fluorophores and can help understand the ligand-binding mechanism of proteins. Among the intrinsic fluorophores of protein, monitoring tryptophan associated fluorescent changes is the most common practice for deriving information regarding the structural changes in protein as well as its dynamics. − BSA consists of two tryptophan residues: the eighth helix of D129–R144, in domain I, contains Trp-134, which is well exposed, whereas Trp-212 is buried inside the protein structure and is present on the second helix of E206-F221 of domain II .…”

Section: Resultsmentioning

confidence: 99%

Evaluation of an Ultrafast Molecular Rotor, Auramine O, as a Fluorescent Amyloid Marker

et al. 2016

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Recently, Auramine O (AuO) has been projected as a fluorescent fibril sensor, and it has been claimed that AuO has an advantage over the most extensively utilized fibril marker, Thioflavin-T (ThT), owing to the presence of an additional large red-shifted emission band for AuO, which was observed exclusively for AuO in the presence of fibrillar media and not in protein or buffer media. As fibrils are very rich in β-sheet structure, a fibril sensor should be more specific toward the β-sheet structure so as to produce a large contrast between the fibril form and native protein form, for efficient detection and in vitro mechanistic studies of fibrillation. However, in this report, we show that AuO interacts significantly with the native form of bovine serum albumin (BSA), which is an all-α-helical protein and lacks the β-sheet structure, which are the hallmarks of a fibrillar structure. This strong interaction of AuO with the native form of BSA leads to a large emission enhancement of AuO for the native protein itself, and leads to a low contrast between the BSA protein and its fibrils. More importantly, the large red-shifted emission band of AuO, reported in the presence of human insulin fibrils, and which was projected as its major advantage over ThT, is not observed in the presence of BSA fibrils as well as fibrils from other proteins, such as lysozyme, human serum albumin, and β-lactoglobulin. Thus, our results provide information on the universal applicability of the distinctive and claimed-to-be-advantageous photophysical features reported for AuO in human insulin fibrils towards fibrils from other proteins. Time-resolved fluorescence measurements also support the proposition of a strong interaction of AuO with native BSA. Additionally, tryptophan emission of the protein has been explored to further elucidate the binding mechanism of AuO with native BSA. Evaluation of thermodynamic parameters revealed that the binding of AuO with native BSA involved positive enthalpy and entropy changes, suggesting dominant contributions from hydrophobic and electrostatic interactions toward the association of AuO with native BSA. Molecular docking calculations have been performed to identify the principal binding location of AuO in native BSA.

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Section: Resultsmentioning

confidence: 99%

Evaluation of an Ultrafast Molecular Rotor, Auramine O, as a Fluorescent Amyloid Marker

et al. 2016

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“…Serum albumin also serves as an internal delivery vehicle for drug molecules, thus, exploited in pharmaceutical research . Bovine serum albumin (BSA) has structural similarity with human serum albumin (HSA), unusual binding affinity with ligands, low cost, easy availability; hence BSA was selected as the model protein to examine their pharmacokinetic relations . Therefore, the BSA‐binding affinities of aroyl hydrazones derivatives L 1 – L 4 were studied theoretically by molecular docking and experimentally by tryptophan quenching.…”

Section: Resultsmentioning

confidence: 99%

Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis, Crystal Structure, Molecular Docking and Their Biological Activities

Kumari

Ansari

Kumar

et al. 2019

Chemistry & Biodiversity

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Here, we report the synthesis and characterization of four new aroyl‐hydrazone derivatives L1–L4, and their structural as well as biological activities have been explored. In addition to docking with bovine serum albumin (BSA) and duplex DNA, the experimental results demonstrate the effective binding of L1–L4 with BSA protein and calf thymus DNA (ct‐DNA) which is in agreement with the docking results. Further biological activities of L1–L4 have been examined through molecular docking with different proteins which are involved in the propagation of viral or cancer diseases. L1 shows best binding affinity with influenza A virus polymerase PB2 subunit (2VY7) with binding energy −11.42 kcal/mol and inhibition constant 4.23 nm, whereas L2 strongly bind with the hepatitis C virus NS5B polymerase (2WCX) with binding energy −10.47 kcal/mol and inhibition constant 21.06 nm. Ligand L3 binds strongly with TGF‐beta receptor 1 (3FAA) and L4 with cancer‐related EphA2 protein kinases (1MQB) with binding energy −10.61 kcal/mol, −10.02 kcal/mol and inhibition constant 16.67 nm and 45.41 nm, respectively. The binding energies of L1–L4 are comparable with binding energies of their proven inhibitors. L1, L3 and L4 can be considered as both 3FAA and 1MQB dual targeting anticancer agents, while L1 and L3 are both 2VY7 and 2WCX dual targeting antiviral agents. On the other side, L2 and L4 target only one virus related target (2WCX). Furthermore, the geometry optimizations of L1–L4 were performed via density functional theory (DFT). Moreover, all four ligands (L1–L4) were characterized by NMR, FT‐IR, ESI‐MS, elemental analysis and their molecular structures were validated by single crystal X‐ray diffraction studies.

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“…Following the same approach, the alteration in the intrinsic fluorescence of warfarin due to its binding in BSA and the subsequent displacement by the addition of divanillin was also studied [ 33 ]. The results depicted in Fig 7 show that phenylbutazone was more effective than ibuprofen in the displacement of warfarin, which proved the efficacy of method for characterization of site I.…”

Section: Resultsmentioning

confidence: 99%

“…The characterisation of the binding site was evaluated by displacement of the fluorescent site markers warfarin [ 33 ] and dansylproline [ 34 ]. For the studies with warfarin (site I), the spectrofluorimeter was adjusted to excitation at 310 nm and emission in the range 330–450 nm.…”

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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Unusual Binding of a Potential Biomarker with Human Serum Albumin

Cited by 15 publications

References 59 publications

Evaluation of an Ultrafast Molecular Rotor, Auramine O, as a Fluorescent Amyloid Marker

Evaluation of an Ultrafast Molecular Rotor, Auramine O, as a Fluorescent Amyloid Marker

Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis, Crystal Structure, Molecular Docking and Their Biological Activities

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

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