Small molecule regulated dynamic structural changes of human G-quadruplexes. Issue 5 (12th February 2016)

• Record Type: Journal Article
• Authors: Debnath, Manish; Ghosh, Shirsendu; Panda, Deepanjan; Bessi, Irene; Schwalbe, Harald; Bhattacharyya, Kankan; Dash, Jyotirmayee
• Is Part Of: Chemical science. Volume 7:Issue 5(2016:May)
• Page Start: 3279
• Page End: 3285
• Publication Date: 2016-02-12
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6sc00057f
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A carbazole derivative (BTC ) regulates the dynamics of unstructured human c-MYC and h-TELO sequences by folding them into compact quadruplex structures. Abstract : The changes in structure and dynamics of oncogenic ( c-MYC ) and telomeric ( h-TELO ) G-rich DNA sequences due to the binding of a novel carbazole derivative (BTC ) are elucidated using single-molecule Förster resonance energy transfer (sm-FRET), fluorescence correlation spectroscopy (FCS) and NMR spectroscopy. In contrast to the previous reports on the binding of ligands to pre-folded G-quadruplexes, this work illustrates how ligand binding changes the conformational equilibria of both unstructured G-rich DNA sequences and K + -folded G-quadruplexes. The results demonstrate that K + free c-MYC and h-TELO exist as unfolded and partially folded conformations. The binding ofBTC shifts the equilibria of both investigated DNA sequences towards the folded G-quadruplex structure, increases the diffusion coefficients and induces faster end-to-end contact formation.BTC recognizes a minor conformation of the c-MYC quadruplex and the two-tetrad basket conformations of the h-TELO quadruplex.