Induced circular dichroism as a tool to monitor the displacement of ligands between albumins

Bertozo, Luiza de Carvalho; Kogut, Małgorzata M.; Maszota‐Zieleniak, Martyna; Samsonov, Sergey A.; Ximenes, Valdecir Farias

doi:10.1016/j.saa.2022.121374

Cited by 4 publications

(8 citation statements)

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“…The prerequisites for an ideal ICD molecule are exciton coupling and a non-chiral molecule with a low-energy barrier for bond rotation. [28][29][30][31] Exciton coupling involves the interaction between two or more chromophores with electric dipoleallowed transitions, typically associated with π-π* transitions. This interaction leads to the formation of an exciton couplet, characterized by two CD bands with opposite signs and similar intensities in the electronic CD spectrum.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, a nonchiral molecule with a lowenergy barrier to rotate a single bond connecting two aromatic rings enables the free rotation of the bond and facilitates conformational changes. [28,29] Notably, the steric hindrance at the binding site acts as a perturbation that restricts the rotation of a single bond and contributes to the generation of ICD signals. Hence, these two prerequisites, exciton coupling and a nonchiral molecule with a low-energy barrier for bond rotation, facilitate the analysis of conformational changes and provide valuable insights into the local environment and interactions at the binding site.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, this “silent region” is advantageous for better signal detection in that spectral range. Second, ICD is highly sensitive to conformational changes, particularly the steric hindrance at the binding site, enabling the detection of subtle structural alterations associated with ligand binding or protein conformational changes [27–29] . Therefore, the robustness of ICD against perturbations and its sensitivity to the local environment makes it a suitable method for local conformational analysis at binding sites, even in crowded environments.…”

Section: Introductionmentioning

confidence: 99%

“…The prerequisites for an ideal ICD molecule are exciton coupling and a non‐chiral molecule with a low‐energy barrier for bond rotation [28–31] . Exciton coupling involves the interaction between two or more chromophores with electric dipole‐allowed transitions, typically associated with π‐π* transitions.…”

Section: Introductionmentioning

confidence: 99%

“…Exciton coupling facilitates the analysis of molecular conformation through the CD spectrum. Moreover, a nonchiral molecule with a low‐energy barrier to rotate a single bond connecting two aromatic rings enables the free rotation of the bond and facilitates conformational changes [28,29] . Notably, the steric hindrance at the binding site acts as a perturbation that restricts the rotation of a single bond and contributes to the generation of ICD signals.…”

Section: Introductionmentioning

confidence: 99%

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Induced Circular Dichroism Analysis of Thermally Induced Conformational Changes on Protein Binding Sites Under a Crowding Environment

Ota,

Konishi,

Tanaka

et al. 2023

ChemPhysChem

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Protein‐ligand interactions in crowded cellular environments play a crucial role in biological functions. The crowded environment can perturb the overall protein structure and local conformation, thereby influencing the binding pathway of protein‐ligand reactions within the cellular milieu. Therefore, a detailed understanding of the local conformation is crucial for elucidating the intricacies of protein‐ligand interactions in crowded cellular environments. In this study, we investigated the feasibility of induced circular dichroism (ICD) using 8‐anilinonaphthalene‐1‐sulfonic acid (ANS) for local conformational analysis at the binding site in crowded environments. Bovine serum albumin (BSA) concentration‐dependent measurements were performed to assess the feasibility of ANS‐ICD for analyzing protein interior binding sites. The results showed distinct changes in the ANS‐ICD spectra of BSA solutions, indicating their potential for analyzing the internal conformation of proteins. Moreover, temperature‐dependent measurements were performed in dilute and crowded environments, revealing distinct denaturation pathways of BSA binding sites. Principal component analysis of ANS‐ICD spectral changes revealed lower temperature pre‐denaturation in the crowded solution than that in the diluted solution, suggesting destabilization of binding sites owing to self‐crowding repulsive interactions. The established ANS‐ICD method can provide valuable conformational insights into protein‐ligand interactions in crowded cellular environments.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Induced Circular Dichroism Analysis of Thermally Induced Conformational Changes on Protein Binding Sites Under a Crowding Environment

Ota,

Konishi,

Tanaka

et al. 2023

ChemPhysChem

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Circular dichroism spectrum of (R)‐(+)‐3,3′‐dibromo‐1,1′‐bi‐2‐naphthol in albumin: Alterations caused by complexation—Experimental and in silico investigation

Ximenes,

Yoguim,

de Souza

et al. 2024

Chirality

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This study describes the interaction of human serum albumin (HSA) with the binol derivative (R)‐(+)‐3,3′‐dibromo‐1,1′‐bi‐2‐naphthol (R‐BrB), which has its optical activity based on the prohibitive energetic barrier for conversion into the enantiomer (S)‐(+)‐3,3′‐dibromo‐1,1′‐bi‐2‐naphthol (S‐BrB). The objective was to assess the ability of HSA to differentiate axial enantiomers based on their binding efficiency and their impact on the CD spectra. We discovered that both enantiomers were effective ligands, and the CD signal disappeared when equimolar amounts of R‐BrB and S‐BrB were simultaneously added, indicating no preference for either enantiomer. The complexation resulted in a significant signal increase at 250 nm and a bathochromic effect at 370 nm. Molecular docking simulations were performed, and the lower energy pose of R‐BrB was selected for DFT calculations. The theoretical CD spectra of free and complexed R‐BrB were obtained and showed alterations corroborating the experimental results. By comparing the difference spectrum (HSA:R‐BrB minus HSA) with the spectrum of free RBrB in water or ethyl alcohol, we concluded that the CD signal intensification was due to the increased solubilization of R‐BrB upon binding to HSA.

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CD, UV, and In Silico Insights on the Effect of 1,3-Bis(1′-uracilyl)-2-propanone on Serum Albumin Structure

et al. 2022

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1,3-diaryl-2-propanone derivatives are synthetic compounds used as building blocks for the realization not only of antimicrobial drugs but also of new nanomaterials thanks to their ability to self-assemble in solution and interact with nucleopeptides. However, their ability to interact with proteins is a scarcely investigated theme considering the therapeutic importance that 1,3-diaryl-2-propanones could have in the modulation of protein-driven processes. Within this scope, we investigated the protein binding ability of 1,3-bis(1′-uracilyl)-2-propanone, which was previously synthesized in our laboratory utilizing a Dakin–West reaction and herein indicated as U2O, using bovine serum albumin (BSA) as the model protein. Through circular dichroism (CD) and UV spectroscopy, we demonstrated that the compound, but not the similar thymine derivative T2O, was able to alter the secondary structure of the serum albumin leading to significant consequences in terms of BSA structure with respect to the unbound protein (Δβ-turn + Δβ-sheet = +23.6%, Δα = −16.7%) as revealed in our CD binding studies. Moreover, molecular docking studies suggested that U2O is preferentially housed in the domain IIIB of the protein, and its affinity for the albumin is higher than that of the reference ligand HA 14−1 (HDOCK score (top 1–3 poses): −157.11 ± 1.38 (U2O); −129.80 ± 6.92 (HA 14−1); binding energy: −7.6 kcal/mol (U2O); −5.9 kcal/mol (HA 14−1)) and T2O (HDOCK score (top 1–3 poses): −149.93 ± 2.35; binding energy: −7.0 kcal/mol). Overall, the above findings suggest the ability of 1,3-bis(1′-uracilyl)-2-propanone to bind serum albumins and the observed reduction of the α-helix structure with the concomitant increase in the β-structure are consistent with a partial protein destabilization due to the interaction with U2O.

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Induced circular dichroism as a tool to monitor the displacement of ligands between albumins

Cited by 4 publications

References 50 publications

Induced Circular Dichroism Analysis of Thermally Induced Conformational Changes on Protein Binding Sites Under a Crowding Environment

Induced Circular Dichroism Analysis of Thermally Induced Conformational Changes on Protein Binding Sites Under a Crowding Environment

Circular dichroism spectrum of (R)‐(+)‐3,3′‐dibromo‐1,1′‐bi‐2‐naphthol in albumin: Alterations caused by complexation—Experimental and in silico investigation

CD, UV, and In Silico Insights on the Effect of 1,3-Bis(1′-uracilyl)-2-propanone on Serum Albumin Structure

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