The characterization and validation of 17β-estradiol binding aptamers

Svobodová, Markéta; Skouridou, Vasso; Botero, Mary Luz; Jauset‐Rubio, Miriam; Schubert, Thomas; Bashammakh, Abdulaziz S.; El-Shahawi, M.S.; Al‐Youbi, Abdulrahman O.; O’Sullivan, Ciara K.

doi:10.1016/j.jsbmb.2016.09.018

Cited by 38 publications

(30 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Looking at the first binding location close to the T‐loop, the total interaction energy is approximately 15 kcal mol −1 weaker than for the A22 aptamer from the work of Alsager et al . This result suggests that the binding of E2 to the A76 aptamer is weaker than to the A22 aptamer, as expected from recent experimental results comparing their binding affinities . Kim et al .…”

Section: Resultsmentioning

confidence: 72%

See 1 more Smart Citation

The Bound Structures of 17β‐Estradiol‐Binding Aptamers

Hilder

Hodgkiss

2017

ChemPhysChem

View full text Add to dashboard Cite

DNA aptamers can exhibit high affinity and selectivity towards their targets, but the aptamer-target complex structures are rarely available from crystallography and often difficult to elucidate. This is particularly true of small molecule targets, including 17β-estradiol (E2), which is becoming one of the most widely encountered endocrine-disrupting chemicals in the environment. Using molecular dynamics simulations, we demonstrate that E2 binds to a thymine loop region common to all E2-specific aptamers in the literature. Analyzing these structures allows us to design new E2 binding sequences. As well as illuminating the essential sequence and structural factors for generating specificity for E2, we demonstrate the effectiveness of molecular dynamics simulations for aptamer science.

show abstract

Section: Resultsmentioning

confidence: 72%

“…Kim et al . and Svobodová et al . determined dissociation constants of 130 and 98 n m , respectively.…”

Section: Resultsmentioning

confidence: 99%

The Bound Structures of 17β‐Estradiol‐Binding Aptamers

Hilder

Hodgkiss

2017

ChemPhysChem

View full text Add to dashboard Cite

show abstract

“…For strong E2−aptamer binding the presence of a loop structure has been stated comprising either T or G bases, where G bases bind more strongly to E2 than T and binding is dominated by van der Waals interactions between aromatic rings present in the E2 molecule and the nucleic acid bases. Several 17β‐estradiol aptamers were compared evaluating their binding properties using different strategies and compare our findings with the literature . Affinity dissociation constants for various 17β‐estradiol aptamers were reported to be in nanomolar range.…”

Section: Introductionmentioning

confidence: 91%

DNA Interaction with 17α‐Ethinylestradiol Studied Using Electrochemical Biosensors and Biosensing in Solution

et al. 2019

View full text Add to dashboard Cite

The synthetic estrogen 17α‐ethinylestradiol (EE2) is an active component of oral contraceptives. It is considered as an endocrine disrupting compound that, once incorporated into an organism, affects the hormonal balance of animals and humans. In this study we characterized the DNA‐EE2 interaction using an electrochemical biosensor and biosensing in solution phase with the double stranded DNA from salmon sperm and deoxyguanosine monophosphate (dGMP). Differential pulse voltammetry method has been applied based on voltammetric anodic responses of the deoxyguanine (dGuo) and deoxyadenine (dAdo) as well as EE2 in the medium of phosphate buffer solution pH 7.0. Binding of EE2 to the nucleobases leads to a decrease of their anodic signals. Association constant for DNA‐EE2 interaction has been estimated to be about 1.1 ⋅ 103 L mol−1 and 1.4 ⋅ 103 L mol−1 for dGuo and dAdo responses, respectively. The association is reversible as indicated by decrease of the EE2 response in pure buffer solution due to leaching of EE2 from the surface attached DNA. The DNA‐EE2 association has been confirmed also by UV‐vis spectrometric experiments.

show abstract

“…SVOBODOVA and colleagues compared and validated different E2-specific aptamers. For the validation process, the techniques microscale thermophoresis, apta-PCR affinity assay and surface plasmon resonance were used [28]. In this study, we chose the E2-specific 35-mer aptamer identified by ALSAGER ET AL.…”

Section: Introductionmentioning

confidence: 99%

“…[17]. This aptamer has already been successfully evaluated in several studies to bind E2 [17,28]. However, there are no crystal or NMR structures available for these aptamers with which an analysis of the interaction between E2 and its specific aptamer would be possible.…”

Section: Introductionmentioning

confidence: 99%

Detailed Analysis of 17β-Estradiol-Aptamer Interactions – A Molecular Dynamics Simulation Study

Eisold

Labudde

2018

Preprint

View full text Add to dashboard Cite

Micro pollutants such as 17β-Estradiol (E2) have been detected in low concentrations in different water resources and their negative effects on the environment and organisms are observed. In this study, a previously described 35-mer E2-specific aptamer was used to investigate the underlying binding characteristics between E2 and the aptamer through an MD simulation in an aqueous medium. There is no 3D structure information for this aptamer, so it was modeled using coarse-grained modeling method. The E2 ligand was positioned inside the potential binding area of the aptamer structure, the underlying complex was used for an 25 ns MD simulation, and the interactions were examined by an interaction profiler tool for each time step. The E2-specific bases of the aptamer had presumably dominant roles in the binding of E2 in terms of the different interaction types. We identified the specific bases within the interior loop of the aptamer and we also demonstrate the influence of oftentimes underestimated water-mediated hydrogen bonds. The study contributes to the understanding of the behavior of ligands binding through aptamer structure in an aqueous solution. The developed workflow allows to generate and examine further appealing ligand aptamer complexes.

show abstract

The characterization and validation of 17β-estradiol binding aptamers

Cited by 38 publications

References 56 publications

The Bound Structures of 17β‐Estradiol‐Binding Aptamers

The Bound Structures of 17β‐Estradiol‐Binding Aptamers

DNA Interaction with 17α‐Ethinylestradiol Studied Using Electrochemical Biosensors and Biosensing in Solution

Detailed Analysis of 17β-Estradiol-Aptamer Interactions – A Molecular Dynamics Simulation Study

Contact Info

Product

Resources

About

The characterization and validation of 17β-estradiol binding aptamers

Cited by 38 publications

References 56 publications

The Bound Structures of 17β‐Estradiol‐Binding Aptamers

The Bound Structures of 17β‐Estradiol‐Binding Aptamers

DNA Interaction with 17α‐Ethinylestradiol Studied Using Electrochemical Biosensors and Biosensing in Solution

Detailed Analysis of 17&beta;-Estradiol-Aptamer Interactions &ndash; A Molecular Dynamics Simulation Study

Contact Info

Product

Resources

About

Detailed Analysis of 17β-Estradiol-Aptamer Interactions – A Molecular Dynamics Simulation Study