Interaction process behind the strong stabilization of G-quadruplexes by alkaloid fagaronine

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biophysical chemistry Pub Date : 2025-04-15 DOI:10.1016/j.bpc.2025.107443

Pavel Hannig , Raimundo Gargallo , Stefania Mazzini , Gigliola Borgonovo , Marco Zuccolo , Eva Táborská , Petr Táborský

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Abstract

Benzo[c]phenanthridine alkaloids are known for their stabilizing effects on non-canonical DNA structures, particularly G-quadruplexes (G4s). In this study, the interaction of fagaronine, a rare benzo[c]phenanthridine alkaloid, with several DNA structures (including B-DNA, parallel, antiparallel and hybrid G4s) is studied using molecular fluorescence and circular dichroism (CD) spectroscopy. It has been found that fagaronine significantly enhances the stability of all tested G4 conformations. Furthermore, a study by NMR spectroscopy provided valuable information on the mechanism of interaction of the ligand with the parallel G4 structure adopted by Pu22T14T23, a sequence mutated with respect to that found within the promoter region of the c-myc gene. Remarkably, when compared with data reported in the literature, fagaronine appears to exhibit one of the strongest G4 thermal stabilization effects ever recorded for a small ligand.

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生物碱法加隆碱强稳定 G-四链体的相互作用过程

苯并[c]菲蒽啶生物碱因其对非典型DNA结构的稳定作用而闻名，特别是g -四聚体（G4s）。本研究利用分子荧光和圆二色性（CD）光谱研究了一种罕见的苯并[c]菲蒽啶生物碱fagaronine与几种DNA结构（包括B-DNA、平行、反平行和杂交G4s）的相互作用。研究发现，fagaronine显著提高了所有测试的G4构象的稳定性。此外，核磁共振波谱研究提供了配体与Pu22T14T23所采用的平行G4结构相互作用机制的宝贵信息，Pu22T14T23是在c-myc基因启动子区域内发现的一个突变序列。值得注意的是，与文献中报道的数据相比，fagaronine似乎表现出有史以来对小配体最强的G4热稳定效应之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biophysical chemistry 生物-生化与分子生物学

CiteScore

6.10

自引率

10.50%

发文量

121

审稿时长

20 days

期刊介绍： Biophysical Chemistry publishes original work and reviews in the areas of chemistry and physics directly impacting biological phenomena. Quantitative analysis of the properties of biological macromolecules, biologically active molecules, macromolecular assemblies and cell components in terms of kinetics, thermodynamics, spatio-temporal organization, NMR and X-ray structural biology, as well as single-molecule detection represent a major focus of the journal. Theoretical and computational treatments of biomacromolecular systems, macromolecular interactions, regulatory control and systems biology are also of interest to the journal.