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Specific Recognition of G-Quadruplexes Over Duplex-DNA by a Macromolecular NIR Two-Photon Fluorescent Probe
The Journal of Physical Chemistry Letters ( IF 4.8 ) Pub Date : 2017-11-22 00:00:00 , DOI: 10.1021/acs.jpclett.7b02547
Marco Deiana 1 , Bastien Mettra 2 , Lara Martinez-Fernandez 3, 4 , Leszek M. Mazur 1 , Krzysztof Pawlik 5 , Chantal Andraud 2 , Marek Samoc 1 , Roberto Improta 3, 4 , Cyrille Monnereau 2 , Katarzyna Matczyszyn 1
Affiliation  

The implication of guanine-rich DNA sequences in biologically important roles such as telomerase dysfunction and the regulation of gene expression has prompted the search for structure-specific G-quadruplex agents for targeted diagnostic and therapeutic applications. Herein, we report on a near-infrared (NIR) two-photon poly(cationic) anthracene-based macromolecule able to selectively target G-quadruplexes (G4s) over genomic double-stranded DNA. In particular, the striking changes in its linear and third-order nonlinear optical properties, combined with the emergence of a strong induced electronic circular dichroism (ECD) signal upon binding to canonical and noncanonical DNA secondary structures allowed for a highly specific detection of several different G4s. Furthermore, through a detailed computational analysis we bring compelling evidence that our probe intercalation within G4s is a thermodynamically favored event, and we fully rationalize the spectroscopic evolution resulting from this complexation event by providing a reasonable explanation regarding the origin of the peculiar ECD effect that accompanies it.

中文翻译:

大分子近红外双光子荧光探针对双链DNA上G-四链体的特异性识别。

富含鸟嘌呤的DNA序列具有重要的生物学作用,例如端粒酶功能障碍和基因表达的调控,这促使人们寻求结构特异性的G-四链体药物,用于靶向诊断和治疗应用。在本文中,我们报道了一种近红外(NIR)两光子聚(阳离子)蒽基大分子,能够选择性地靶向基因组双链DNA上的G-四链体(G4s)。特别是,其线性和三阶非线性光学特性发生了惊人的变化,并结合了规范的和非规范的DNA二级结构后,出现了强烈的诱导电子圆二色性(ECD)信号,从而可以对几种不同的化合物进行高度特异性的检测G4s。此外,
更新日期:2017-11-22
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