High-Resolution Insight into G-Overhang Architecture

J 2013

High-Resolution Insight into G-Overhang Architecture

HAENSEL, Robert, Frank LOEHR, Lukáš TRANTÍREK and Volker DOETSCH

Basic information

Original name

High-Resolution Insight into G-Overhang Architecture

Authors

HAENSEL, Robert (276 Germany), Frank LOEHR (276 Germany), Lukáš TRANTÍREK (203 Czech Republic, guarantor, belonging to the institution) and Volker DOETSCH (276 Germany)

Edition

Journal of the American Chemical Society, Washington, American Chemical Society, 2013, 0002-7863

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 11.444

RIV identification code

RIV/00216224:14740/13:00072647

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1021/ja312403b

UT WoS

000315373000062

Keywords in English

HUMAN TELOMERIC DNA; INTRAMOLECULAR G-QUADRUPLEX; K+ SOLUTION; NMR-SPECTROSCOPY; SMALL-MOLECULE; HUMAN CANCER; PULSED EPR; STABILITY; SEQUENCE; CONFORMATIONS

Abstract

V originále

NMR and fluorescence spectroscopy were used to address the effect of intracellular molecular crowding and related hydration on a model telomeric G-quadruplex (G4) DNA structure (d(AG(3)(TTAGGG)(3))). d(AG(3)(TTAGGG)(3)) prevalently adopted the hybrid-1 conformation in vivo, ex vivo, and in dilute potassium-based solution, while it formed the parallel propeller fold in water-depleted potassium-based solution, a commonly used model system for studying intracellular molecular crowding. The dilute potassium-based solution appeared to imitate the properties of the cellular environment required for d(AG(3)(TTAGGG)(3)) folding under in vivo and ex vivo conditions. High-resolution NMR investigations of site-specifically N-15-labeled G4 units in native-like single-stranded telomeric DNA revealed that the 3'-terminal and internal G4 unit predominantly coexist in 2-tetrad antiparallel basket and hybrid-2 structures that are arranged in "beads-on-a-string"-like fashion. Our data provide the first high-resolution insight into the telomeric G-overhang architecture under essentially physiological conditions and identify the 2-tetrad antiparallel basket and hybrid-2 topologies as the structural targets for the development of telomere-specific G4 ligands.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Citovat

HAENSEL, Robert, Frank LOEHR, Lukáš TRANTÍREK and Volker DOETSCH. High-Resolution Insight into G-Overhang Architecture. Journal of the American Chemical Society. Washington: American Chemical Society, 2013, vol. 135, No 7, p. 2816-2824. ISSN 0002-7863. Available from: https://dx.doi.org/10.1021/ja312403b.

@article{1169515,
   author = {Haensel, Robert and Loehr, Frank and Trantírek, Lukáš and Doetsch, Volker},
   article_location = {Washington},
   article_number = {7},
   doi = {http://dx.doi.org/10.1021/ja312403b},
   keywords = {HUMAN TELOMERIC DNA; INTRAMOLECULAR G-QUADRUPLEX; K+ SOLUTION; NMR-SPECTROSCOPY; SMALL-MOLECULE; HUMAN CANCER; PULSED EPR; STABILITY; SEQUENCE; CONFORMATIONS},
   language = {eng},
   issn = {0002-7863},
   journal = {Journal of the American Chemical Society},
   title = {High-Resolution Insight into G-Overhang Architecture},
   volume = {135},
   year = {2013}
}

TY  - JOUR
ID  - 1169515
AU  - Haensel, Robert - Loehr, Frank - Trantírek, Lukáš - Doetsch, Volker
PY  - 2013
TI  - High-Resolution Insight into G-Overhang Architecture
JF  - Journal of the American Chemical Society
VL  - 135
IS  - 7
SP  - 2816-2824
EP  - 2816-2824
PB  - American Chemical Society
SN  - 00027863
KW  - HUMAN TELOMERIC DNA
KW  - INTRAMOLECULAR G-QUADRUPLEX
KW  - K+ SOLUTION
KW  - NMR-SPECTROSCOPY
KW  - SMALL-MOLECULE
KW  - HUMAN CANCER
KW  - PULSED EPR
KW  - STABILITY
KW  - SEQUENCE
KW  - CONFORMATIONS
N2  - NMR and fluorescence spectroscopy were used to address the effect of intracellular molecular crowding and related hydration on a model telomeric G-quadruplex (G4) DNA structure (d(AG(3)(TTAGGG)(3))). d(AG(3)(TTAGGG)(3)) prevalently adopted the hybrid-1 conformation in vivo, ex vivo, and in dilute potassium-based solution, while it formed the parallel propeller fold in water-depleted potassium-based solution, a commonly used model system for studying intracellular molecular crowding. The dilute potassium-based solution appeared to imitate the properties of the cellular environment required for d(AG(3)(TTAGGG)(3)) folding under in vivo and ex vivo conditions. High-resolution NMR investigations of site-specifically N-15-labeled G4 units in native-like single-stranded telomeric DNA revealed that the 3'-terminal and internal G4 unit predominantly coexist in 2-tetrad antiparallel basket and hybrid-2 structures that are arranged in "beads-on-a-string"-like fashion. Our data provide the first high-resolution insight into the telomeric G-overhang architecture under essentially physiological conditions and identify the 2-tetrad antiparallel basket and hybrid-2 topologies as the structural targets for the development of telomere-specific G4 ligands.
ER  -

HAENSEL, Robert, Frank LOEHR, Lukáš TRANTÍREK and Volker DOETSCH. High-Resolution Insight into G-Overhang Architecture. \textit{Journal of the American Chemical Society}. Washington: American Chemical Society, 2013, vol.~135, No~7, p.~2816-2824. ISSN~0002-7863. Available from: https://dx.doi.org/10.1021/ja312403b.

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