Spectroscopic studies on noncovalent binding of nicotinamide–modified BRCA1 (856–871) analogs to calf thymus DNA

Pan, Boyuan; Lv, Mingxiu; Du, Heng; Zhao, Dongxin; Lü, Kui

doi:10.1016/j.saa.2023.122531

Cited by 2 publications

(3 citation statements)

References 44 publications

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“…Both signals are increased and shifted as a result of the small molecule’s intercalative binding to DNA, which stabilizes the B-form of DNA. Accordingly, to simple groove binding, electrostatic binding also causes little to no perturbation on the bands. , Both the negative and positive bands′ intensities are considerably reduced in this instance (shifting to level zero). However, the minimal perturbation to the positive band is greater than that to the negative band, indicating that the presence of YH has little to no impact on the CT-DNA helicity .…”

Section: Resultsmentioning

confidence: 77%

“…The development of single-stranded DNA is referred to as thermal melting ( T m ) of DNA and occurs when the structural stability of double-stranded DNA is disrupted by altering the temperature. The temperature upon which 50% of all bases are exposed to ultraviolet light is known as the thermal melting temperature ( T m ). , The melting temperature ( T m ) typically increases significantly when an intercalation-based binding mechanism of a small molecule with DNA is used. In addition, groove binding and electrostatic binding to the DNA phosphate backbone result in a slight shift in T m values. , …”

Section: Resultsmentioning

confidence: 99%

“…The temperature upon which 50% of all bases are exposed to ultraviolet light is known as the thermal melting temperature (T m ). 40,41 The melting temperature (T m ) typically increases significantly when an intercalation-based binding mechanism of a small molecule with DNA is used. In addition, groove binding and electrostatic binding to the DNA phosphate backbone result in a slight shift in T m values.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Structural Insight into Groove Binding of Yohimbine with Calf Thymus DNA: A Spectroscopic, Calorimetric, and Computational Approach

et al. 2023

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A variety of anticancer and antibacterial drugs target DNA as one of their primary intracellular targets. Understanding ligand−DNA interactions and developing new, promising bioactive molecules for clinical use are greatly aided by elucidating the interaction between small molecules and natural polymeric DNAs. Small molecules′ ability to attach to and inhibit DNA replication and transcription provides more information on how drugs impact the expression of genes. Yohimbine has been broadly studied in pharmacological properties, while its binding mode to DNA has not been explicated so far. In this study, an attempt was made to explore the interaction between Yohimbine (YH) and calf thymus (CT-DNA) by using varying thermodynamics and in silico approaches. Minor hypochromic and bathochromic shifts of fluorescence intensity were observed, suggesting the binding of YH to CT-DNA. The Scatchard plot analysis using the McGhee−von Hipple method revealed noncooperative binding and affinities in the range of 10 5 M −1 . The binding stoichiometry value is 2:1 (2 molecules of YH were span by 1 base pair) and was determined by Job's plot. The thermodynamic parameters suggested exothermic binding, which was favored by negative enthalpy and positive entropy changes from both isothermal titration calorimetry and temperature-dependent fluorescence experiment. Salt-dependent fluorescence suggested that the interaction between the ligand and DNA was governed by nonpolyelectrolytic forces. Kinetics experiment confirmed the static type of quenching. The results of iodide quenching, urea denaturation assay, dye displacement, DNA melting, and in silico molecular docking (MD) suggested groove binding of YH to CT-DNA. Circular dichroism spectra confirmed minimal perturbation of CT-DNA with YH binding via groove region. Therefore, the groove binding mechanism of interaction was validated by biophysical techniques and in silico, MD approaches. The findings supported here may contribute to the development of new YH therapeutics possessing better efficacy and lesser side effects.

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Section: Resultsmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Structural Insight into Groove Binding of Yohimbine with Calf Thymus DNA: A Spectroscopic, Calorimetric, and Computational Approach

et al. 2023

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Into the Groove: A Multitechnique Insight into the DNA–Vemurafenib Interaction

Cavalieri,

Pison,

Marson

et al. 2024

Applied Biosciences

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This study explores the interaction between Vemurafenib (VEM), a potent BRAF inhibitor, and calf thymus DNA (ctDNA) using a comprehensive array of biophysical and computational techniques. The primary objective is to understand the potential off-target effects of VEM on DNA, given its established role in melanoma therapy targeting the BRAF V600E mutation. The investigation employed methods such as ultraviolet–visible absorption spectroscopy, steady-state fluorescence, circular dichroism, isothermal titration calorimetry, and advanced molecular dynamics simulations. The results indicate that VEM interacts with DNA primarily through a minor groove-binding mechanism, causing minimal structural disruption to the DNA double helix. Viscosity measurements and melting temperature analyses further confirmed this non-intercalative mode of binding. Calorimetry data revealed an exothermic, thermodynamically favorable interaction between VEM and ctDNA, driven by both enthalpic and entropic factors. Finally, computer simulations identified the most probable binding site and mode of VEM within the minor groove of the nucleic acid, providing a molecular basis for the experimental findings.

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Spectroscopic studies on noncovalent binding of nicotinamide–modified BRCA1 (856–871) analogs to calf thymus DNA

Cited by 2 publications

References 44 publications

Structural Insight into Groove Binding of Yohimbine with Calf Thymus DNA: A Spectroscopic, Calorimetric, and Computational Approach

Structural Insight into Groove Binding of Yohimbine with Calf Thymus DNA: A Spectroscopic, Calorimetric, and Computational Approach

Into the Groove: A Multitechnique Insight into the DNA–Vemurafenib Interaction

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