title: Structure conversion and structure separation of G-quadruplexes investigated by carbazole derivatives.
abstract: The challenge of G-quadruplexes is that the G-rich sequences can adopt various G4 structures and possibly interconvert among them, particularly under the change of environmental conditions. Both NMR and circular dichroism (CD) show the spectral conversion of d[AG3(T2AG3)3] (HT22) from Na-form to K-form after Na+/K+ ion exchange. No appreciable change on the induced CD spectra of BMVC molecule and the single molecule tethered particle motion of HT22 in Na+ solution upon K+ titration suggests that the spectral conversion is unlikely due to the structural conversion via fully unfolded intermediate. Although a number of mechanisms were proposed for the spectral change induced by the Na+/K+ ion exchange, determining the precise structures of HT22 in K+ solution may be essential to unravel the mechanism of the structural conversion. Thus, development of a new method for separating different structures is of critical importance for further individual verification. In the second part of this review, we describe a new approach based on "micelle-enhanced ultrafiltration" method for DNA structural separation. The BMVC, a G-quadruplex ligand, is first modified and then forms a large size of emulsion after ultrasonic emulsification, together with its different binding affinities to various DNA structures; for the first time, we are able to separate different DNA structures after membrane filtration. Verification of the possible structural conversion and investigation of structural diversity among various G4 structures are essential for exploring their potential biological roles and for developing new anticancer drugs.
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, Taiwan, Republic of China. tcchang@po.iams.sinica.edu.tw
authors.forename: Ta-Chau
authors.initials: TC
authors.lastname: Chang
authors.forename: Jen-Fei
authors.initials: JF
authors.lastname: Chu
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Tsai
authors.forename: Zi-Fu
authors.initials: ZF
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D055808:Drug Discovery; D004655:Emulsions; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D013696:Temperature; D014462:Ultrafiltration
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D004655:Emulsions; D008024:Ligands; D008823:Micelles; D004247:DNA