Raju G, Srinivas R, Reddy M Damoder, Reddy Ch Raji, Nagesh N
a National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
Nucleosides Nucleotides Nucleic Acids. 2014;33(7):489-506. doi: 10.1080/15257770.2014.891742.
In the present study, electrospray ionization mass spectrometry (ESI-MS) and spectroscopy have been used to evaluate the non-covalent interaction, stoichiometry, and selectivity of two synthetic coumarin-attached nucleoside and non-nucleoside 1,2,3-triazoles, namely, (1-(5-(hydroxymethyl)-4-(4-((2-oxo-2H-chromen-4-yloxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-furan-2-yl)5-methyl pyrimidine-2,4(1H,3H)-dione (Tr1) and 4-((1-((-1-methyl-1H-indol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (Tr2) with two different human telomeric intermolecular G-quadruplex DNA structures formed by d(T2AG3) and d(T2AG3)2 sequences. ESI-MS studies indicate that Tr1 specifically interacts with four-stranded intermolecular parallel quadruplex complex, whereas Tr2 interacts with two hairpin as well as four-stranded intermolecular parallel quadruplex complexes. UV-Visible spectroscopic studies suggest that Tr1 and Tr2 interact with G-quadruplex structure and unwind them. Job plots show that stoichiometry of ligand:quadruplex DNA is 1:1. Circular dichroism (CD) studies of G-quadruplex DNA and Tr1/Tr2 ligands manifest that they unfold DNA on interaction. Fluorescence studies demonstrate that ligand molecules intercalate between the two stacks of quadruplex DNA and non-radiative energy transfer occurs between the excited ligand molecules (donor) and quadruplex DNA (acceptor), resulting in enhancement of fluorescence emission intensity. Thus, these studies suggest that nucleoside and non-nucleoside ligands efficiently interact with d(T2AG3) and d(T2AG3)2 G-quadruplex DNA but the interaction is not alike with all kinds of quadruplex DNA, this is probably due to the variation in the pharmacophores and structure of the ligand molecules.
在本研究中，电喷雾电离质谱（ESI-MS）和光谱法已被用于评估两种合成的香豆素连接的核苷和非核苷1,2,3-三唑，即(1-(5-(羟甲基)-4-(4-((2-氧代-2H-色烯-4-基氧基)甲基)-1H-1,2,3-三唑-1-基)四氢呋喃-2-基)5-甲基嘧啶-2,4(1H,3H)-二酮（Tr1）和4-((1-((-1-甲基-1H-吲哚-2-基)甲基)-1H-1,2,3-三唑-4-基)甲氧基)-2H-色烯-2-酮（Tr2）与由d(T2AG3)和d(T2AG3)2序列形成的两种不同的人端粒分子间G-四链体DNA结构的非共价相互作用、化学计量比和选择性。ESI-MS研究表明，Tr1与四链体分子间平行四链体复合物特异性相互作用，而Tr2与两个发夹以及四链体分子间平行四链体复合物相互作用。紫外可见光谱研究表明，Tr1和Tr2与G-四链体结构相互作用并使其解旋。工作曲线表明配体：四链体DNA的化学计量比为1:1。G-四链体DNA和Tr1/Tr2配体的圆二色性（CD）研究表明，它们在相互作用时使DNA解折叠。荧光研究表明，配体分子插入四链体DNA的两层堆积之间，并且在激发的配体分子（供体）和四链体DNA（受体）之间发生非辐射能量转移，导致荧光发射强度增强。因此，这些研究表明核苷和非核苷配体与d(T2AG3)和d(T2AG3)2 G-四链体DNA有效相互作用，但这种相互作用并非与所有类型的四链体DNA都相同，这可能是由于配体分子的药效基团和结构存在差异。
