Designing a New Class of Bases for Nucleic Acid Quadruplexes
and Quadruplex-Active Ligands

J 2015

Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands

BAZZI, Sophia, Jan NOVOTNÝ, Yevgen YURENKO and Radek MAREK

Basic information

Original name

Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands

Authors

BAZZI, Sophia (364 Islamic Republic of Iran, belonging to the institution), Jan NOVOTNÝ (203 Czech Republic, belonging to the institution), Yevgen YURENKO (804 Ukraine, belonging to the institution) and Radek MAREK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Chemistry - A European Journal, Weinheim, Wiley-VCH, 2015, 0947-6539

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10403 Physical chemistry

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

DOI: 10.1002/chem.201500743

Impact factor

Impact factor: 5.771

RIV identification code

RIV/00216224:14740/15:00082881

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1002/chem.201500743

UT WoS

000356795000020

Keywords in English

Density functional calculations; DNA; G-quadruplexes; ligand design; nucleobases

Abstract

V originále

A new class of quadruplex nucleobases, derived from 3-deazaguanine, has been designed for various applications as smart quadruplex ligands as well as quadruplex-based aptamers, receptors, and sensors. An efficient strategy for modifying the guanine quadruplex core has been developed and tested by using quantum chemistry methods. Several potential guanine derivatives modified at the 3- or 8-position or both are analyzed, and the results compared to reference systems containing natural guanine. Analysis of the formation energies (BLYP-D3(BJ)/def2-TZVPP level of theory, in combination with the COSMO model for water) in model systems consisting of two and three stacked tetrads with Na+/K+ ion(s) inside the internal channel indicates that the formation of structures with 3-halo-3-deazaguanine bases leads to a substantial gain in energy, as compared to the corresponding reference guanine complexes. The results cast light on changes in the noncovalent interactions (hydrogen bonding, stacking, and ion coordination) in a quadruplex stem upon modification of the guanine core. In particular, the enhanced stability of the modified quadruplexes was shown to originate mainly from increased pi–pi stacking. Our study suggests the 3-halo-3-deazaguanine skeleton as a potential building unit for quadruplex systems and smart G-quadruplex ligands.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

286154, interní kód MU

Name: SYLICA - Synergies of Life and Material Sciences to Create a New Future (Acronym: SYLICA)

Investor: European Union, Capacities

Citovat

BAZZI, Sophia, Jan NOVOTNÝ, Yevgen YURENKO and Radek MAREK. Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands. Chemistry - A European Journal. Weinheim: Wiley-VCH, 2015, vol. 21, No 26, p. 9414-9425. ISSN 0947-6539. Available from: https://dx.doi.org/10.1002/chem.201500743.

@article{1299450,
   author = {Bazzi, Sophia and Novotný, Jan and Yurenko, Yevgen and Marek, Radek},
   article_location = {Weinheim},
   article_number = {26},
   doi = {http://dx.doi.org/10.1002/chem.201500743},
   keywords = {Density functional calculations; DNA; G-quadruplexes; ligand design; nucleobases},
   language = {eng},
   issn = {0947-6539},
   journal = {Chemistry - A European Journal},
   title = {Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands},
   url = {http://dx.doi.org/10.1002/chem.201500743},
   volume = {21},
   year = {2015}
}

TY  - JOUR
ID  - 1299450
AU  - Bazzi, Sophia - Novotný, Jan - Yurenko, Yevgen - Marek, Radek
PY  - 2015
TI  - Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands
JF  - Chemistry - A European Journal
VL  - 21
IS  - 26
SP  - 9414-9425
EP  - 9414-9425
PB  - Wiley-VCH
SN  - 09476539
KW  - Density functional calculations
KW  - DNA
KW  - G-quadruplexes
KW  - ligand design
KW  - nucleobases
UR  - http://dx.doi.org/10.1002/chem.201500743
L2  - http://dx.doi.org/10.1002/chem.201500743
N2  - A new class of quadruplex nucleobases, derived from 3-deazaguanine, has been designed for various applications as smart quadruplex ligands as well as quadruplex-based aptamers, receptors, and sensors. An efficient strategy for modifying the guanine quadruplex core has been developed and tested by using quantum chemistry methods. Several potential guanine derivatives modified at the 3- or 8-position or both are analyzed, and the results compared to reference systems containing natural guanine. Analysis of the formation energies (BLYP-D3(BJ)/def2-TZVPP level of theory, in combination with the COSMO model for water) in model systems consisting of two and three stacked tetrads with Na+/K+ ion(s) inside the internal channel indicates that the formation of structures with 3-halo-3-deazaguanine bases leads to a substantial gain in energy, as compared to the corresponding reference guanine complexes. The results cast light on changes in the noncovalent interactions (hydrogen bonding, stacking, and ion coordination) in a quadruplex stem upon modification of the guanine core. In particular, the enhanced stability of the modified quadruplexes was shown to originate mainly from increased pi–pi stacking. Our study suggests the 3-halo-3-deazaguanine skeleton as a potential building unit for quadruplex systems and smart G-quadruplex ligands.
ER  -

BAZZI, Sophia, Jan NOVOTNÝ, Yevgen YURENKO and Radek MAREK. Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands. \textit{Chemistry - A European Journal}. Weinheim: Wiley-VCH, 2015, vol.~21, No~26, p.~9414-9425. ISSN~0947-6539. Available from: https://dx.doi.org/10.1002/chem.201500743.

Detailed Information on Publication Record