title: Studies on non-covalent interaction of coumarin attached pyrimidine and 1-methyl indole 1,2,3 triazole analogues with intermolecular telomeric G-quadruplex DNA using ESI-MS and spectroscopy.
abstract: 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.
authors: a National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology , Hyderabad , India.
authors: G
authors: G
authors: Raju
authors: R
authors: R
authors: Srinivas
authors: M Damoder
authors: MD
authors: Reddy
authors: Ch Raji
authors: ChR
authors: Reddy
authors: N
authors: N
authors: Nagesh
mesh_terms: D003374:Coumarins / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D007211:Indoles / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013057:Spectrum Analysis; D016615:Telomere / Q000235:genetics*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D003374:Coumarins; D007211:Indoles; D011743:Pyrimidines; D014230:Triazoles; C022957:1-methylindole; D004247:DNA; C030123:coumarin; C030986:pyrimidine
keywords: ESI-MS; G-quadruplex DNA; G-quadruplex DNA interaction; nucleoside and non-nucleoside ligands; spectroscopy