Asymmetric Distyrylpyridinium Dyes as Red‐Emitting Fluorescent Probes for Quadruplex DNA |
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Authors: | Xiao Xie Bina Choi Dr. Eric Largy Dr. Régis Guillot Dr. Anton Granzhan Dr. Marie‐Paule Teulade‐Fichou |
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Affiliation: | 1. CNRS UMR176, Institut Curie, Centre de Recherche, 91405 Orsay (France);2. Exchange student from the Massachusetts Institute of Technology, Cambridge MA (USA);3. CNRS UMR8182, Institut de Chimie Moléculaire et des Matériaux d'Orsay, Université Paris‐Sud XI, 91405 Orsay (France) |
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Abstract: | The interactions of three cationic distyryl dyes, namely 2,4‐bis(4‐dimethylaminostyryl)‐1‐methylpyridinium ( 1 a ), its derivative with a quaternary aminoalkyl chain ( 1 b ), and the symmetric 2,6‐bis(4‐dimethylaminostyryl)‐1‐methylpyridinium ( 2 a ), with several quadruplex and duplex nucleic acids were studied with the aim to establish the influence of the geometry of the dyes on their DNA‐binding and DNA‐probing properties. The results from spectrofluorimetric titrations and thermal denaturation experiments provide evidence that asymmetric (2,4‐disubstituted) dyes 1 a and 1 b bind to quadruplex DNA structures with a near‐micromolar affinity and a fair selectivity with respect to double‐stranded (ds) DNA [Ka(G4)/Ka(ds)=2.5–8.4]. At the same time, the fluorescence of both dyes is selectively increased in the presence of quadruplex DNAs (more than 80–100‐fold in the case of human telomeric quadruplex), even in the presence of an excess of competing double‐stranded DNA. This optical selectivity allows these dyes to be used as quadruplex‐DNA‐selective probes in solution and stains in polyacrylamide gels. In contrast, the symmetric analogue 2 a displays a strong binding preference for double‐stranded DNA [Ka(ds)/Ka(G4)=40–100), presumably due to binding in the minor groove. In addition, 2 a is not able to discriminate between quadruplex and duplex DNA, as its fluorescence is increased equally well (20–50‐fold) in the presence of both structures. This study emphasizes and rationalizes the strong impact of subtle structural variations on both DNA‐recognition properties and fluorimetric response of organic dyes. |
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Keywords: | DNA recognition dyes/pigments electrophoresis fluorescent probes quadruplex DNA |
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