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Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs

DNA interactions with multivalent ligand(s) have increasingly become the subject of substantial research. For several small molecules with therapeutic potential, nucleic acids serve as their primary molecular target. Such interaction has been shown to affect transcription or replication, ultimately...

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Autores principales: Luikham, Soching, Yanthan, Senchumbeni, Bhattacharyya, Jhimli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10509242/
https://www.ncbi.nlm.nih.gov/pubmed/37726357
http://dx.doi.org/10.1038/s41598-023-40713-5
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author Luikham, Soching
Yanthan, Senchumbeni
Bhattacharyya, Jhimli
author_facet Luikham, Soching
Yanthan, Senchumbeni
Bhattacharyya, Jhimli
author_sort Luikham, Soching
collection PubMed
description DNA interactions with multivalent ligand(s) have increasingly become the subject of substantial research. For several small molecules with therapeutic potential, nucleic acids serve as their primary molecular target. Such interaction has been shown to affect transcription or replication, ultimately leading to apoptotic cell death. As a result, researchers are becoming increasingly interested in understanding how small molecules interact with DNA making it possible to develop new, DNA-specific drugs. The bioactive indole alkaloid, Yohimbe (Yohimbine; Yh) has been broadly studied in pharmacological properties while its binding mode to DNA has not been explicated so far. This study adopted molecular modelling and multi-spectroscopic methods to investigate the interaction between Yohimbine and herring testes (HT DNA) in physiological conditions. Minor hypochromic and bathochromic shifts of fluorescence intensity were observed, suggesting the binding of Yh to HT DNA. The Scatchard plot analyses using the McGhee-von Hipple method revealed non-cooperative binding and affinities in the range of 10(5) M(−1). The thermodynamic parameters suggested exothermic binding, which was favoured by negative enthalpy and positive entropy changes from temperature-dependent fluorescence experiments. Salt-dependent fluorescence suggested that the interaction between the ligand and DNA was governed by non-polyelectrolytic forces. The results of iodide quenching, urea denaturation assay, dye displacement, and in silico molecular docking, suggested groove binding of Yh to HT DNA. Thus, the groove binding mechanism of interaction was validated by both biophysical and computational techniques. The structural elucidation and energetic profiling of Yh's interaction with naturally occurring polymeric DNA can be useful to the development of DNA-targeted therapeutics.
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spelling pubmed-105092422023-09-21 Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs Luikham, Soching Yanthan, Senchumbeni Bhattacharyya, Jhimli Sci Rep Article DNA interactions with multivalent ligand(s) have increasingly become the subject of substantial research. For several small molecules with therapeutic potential, nucleic acids serve as their primary molecular target. Such interaction has been shown to affect transcription or replication, ultimately leading to apoptotic cell death. As a result, researchers are becoming increasingly interested in understanding how small molecules interact with DNA making it possible to develop new, DNA-specific drugs. The bioactive indole alkaloid, Yohimbe (Yohimbine; Yh) has been broadly studied in pharmacological properties while its binding mode to DNA has not been explicated so far. This study adopted molecular modelling and multi-spectroscopic methods to investigate the interaction between Yohimbine and herring testes (HT DNA) in physiological conditions. Minor hypochromic and bathochromic shifts of fluorescence intensity were observed, suggesting the binding of Yh to HT DNA. The Scatchard plot analyses using the McGhee-von Hipple method revealed non-cooperative binding and affinities in the range of 10(5) M(−1). The thermodynamic parameters suggested exothermic binding, which was favoured by negative enthalpy and positive entropy changes from temperature-dependent fluorescence experiments. Salt-dependent fluorescence suggested that the interaction between the ligand and DNA was governed by non-polyelectrolytic forces. The results of iodide quenching, urea denaturation assay, dye displacement, and in silico molecular docking, suggested groove binding of Yh to HT DNA. Thus, the groove binding mechanism of interaction was validated by both biophysical and computational techniques. The structural elucidation and energetic profiling of Yh's interaction with naturally occurring polymeric DNA can be useful to the development of DNA-targeted therapeutics. Nature Publishing Group UK 2023-09-19 /pmc/articles/PMC10509242/ /pubmed/37726357 http://dx.doi.org/10.1038/s41598-023-40713-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Luikham, Soching
Yanthan, Senchumbeni
Bhattacharyya, Jhimli
Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs
title Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs
title_full Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs
title_fullStr Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs
title_full_unstemmed Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs
title_short Mechanistic investigation into the binding property of Yohimbe towards natural polymeric DNAs
title_sort mechanistic investigation into the binding property of yohimbe towards natural polymeric dnas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10509242/
https://www.ncbi.nlm.nih.gov/pubmed/37726357
http://dx.doi.org/10.1038/s41598-023-40713-5
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