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Nucleic Acids Res. 2018 May 4;46(8):4301-4315. doi: 10.1093/nar/gky250.

Pursuing origins of (poly)ethylene glycol-induced G-quadruplex structural modulations.

Author information

1
Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, Ljubljana, SI-1000, Slovenia.
2
Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
3
Department of Computational Science, Graduate School of System Informatics, Kobe University, 1-1, Rokkodai, Nada-ku, Kobe 657-8501, Japan.
4
EN→FIST Centre of Excellence, Trg OF 13, SI-1000 Ljubljana, Slovenia.
5
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, p. p. 537, SI-1000 Ljubljana, Slovenia.
6
Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Kobe 650-0047, Japan.

Abstract

Molecular crowding conditions provided by high concentration of cosolutes are utilized for characterization of biomolecules in cell-mimicking environment and development of drug-delivery systems. In this context, (poly)ethylene glycols are often used for studying non-canonical DNA structures termed G-quadruplexes, which came into focus by emerging structural biology findings and new therapeutic drug design approaches. Recently, several reports were made arguing against using (poly)ethylene glycols in role of molecular crowding agents due to their direct impact on DNA G-quadruplex stability and topology. However, the available data on structural details underlying DNA interaction is very scarce and thus limits in-depth comprehension. Herein, structural and thermodynamic analyses were strategically combined to assess G-quadruplex-cosolute interactions and address previously reported variances regarding the driving forces of G-rich DNA structural transformations under molecular crowding conditions. With the use of complementary (CD, NMR and UV) spectroscopic methods and model approach we characterized DNA G-quadruplex in the presence of the smallest and one of the largest typically used (poly)ethylene glycols. Dehydration effect is the key contributor to ethylene-glycol-induced increased stability of the G-quadruplex, which is in the case of the large cosolute mainly guided by the subtle direct interactions between PEG 8000 and the outer G-quartet regions.

PMID:
29648656
PMCID:
PMC5934638
DOI:
10.1093/nar/gky250
[Indexed for MEDLINE]
Free PMC Article

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