Structural and energetic properties of the potential HIV-1
reverse transcriptase inhibitors d4A and d4G: a comprehensive
theoretical investigation

J 2014

Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation

PONOMAREVA, Alla, Yevgen YURENKO, Roman ZHURAKIVSKY, Tanja VAN MOURIK, Dmytro HOVORUN et. al.

Basic information

Original name

Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation

Authors

PONOMAREVA, Alla (804 Ukraine), Yevgen YURENKO (804 Ukraine, guarantor, belonging to the institution), Roman ZHURAKIVSKY (804 Ukraine), Tanja VAN MOURIK (528 Netherlands) and Dmytro HOVORUN (804 Ukraine)

Edition

Journal of Biomolecular Structure and Dynamics, Philadelphia, Taylor & Francis, 2014, 0739-1102

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10403 Physical chemistry

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.919

RIV identification code

RIV/00216224:14740/14:00074813

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1080/07391102.2013.789401

UT WoS

000331525100005

Keywords in English

2 ' 3 ' -didehydro-2' 3 ' -dideoxyadenosine; 2 ' 3 ' -didehydro-2 ' 3 ' -dideoxyguanosine; d4A; d4G; conformational analysis; hydrogen bonds; H-bonds; biological activity; nucleoside reverse transcriptase inhibitors; density functional theory

Abstract

V originále

A comprehensive quantum-chemical investigation of the conformational landscapes of two nucleoside HIV-1 reverse transcriptase inhibitors, d4A and d4G, has been performed. Both nucleosides are shaped by a sophisticated network of specific noncovalent interactions, including conventional OH_O, NH_O and weak CH_O, CH_N hydrogen bonds, as well as dihydrogen CH_HC contacts. For the OH_O, NH_O, and CH_O hydrogen bonds, natural bond orbital analysis revealed hyperconjugative interactions between the oxygen lone pairs and the antibonding orbital of the donor group. For the CH _HC contacts, the electron density migrates from the antibonding orbital, corresponding to the CH group of the sugar residue, to the bonding orbital relative to the same group in the nucleobase. The results confirm the current belief that the biological activity of d4A and d4G is connected with the termination of the DNA chain synthesis. Thus, these nucleosides act as competitive HIV-1 reverse transcriptase inhibitors.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Citovat

PONOMAREVA, Alla, Yevgen YURENKO, Roman ZHURAKIVSKY, Tanja VAN MOURIK and Dmytro HOVORUN. Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation. Journal of Biomolecular Structure and Dynamics. Philadelphia: Taylor & Francis, 2014, vol. 32, No 5, p. 730-740. ISSN 0739-1102. Available from: https://dx.doi.org/10.1080/07391102.2013.789401.

@article{1129505,
   author = {Ponomareva, Alla and Yurenko, Yevgen and Zhurakivsky, Roman and van Mourik, Tanja and Hovorun, Dmytro},
   article_location = {Philadelphia},
   article_number = {5},
   doi = {http://dx.doi.org/10.1080/07391102.2013.789401},
   keywords = {2 ' 3 ' -didehydro-2' 3 ' -dideoxyadenosine; 2 ' 3 ' -didehydro-2 ' 3 ' -dideoxyguanosine; d4A; d4G; conformational analysis; hydrogen bonds; H-bonds; biological activity; nucleoside reverse transcriptase inhibitors; density functional theory},
   language = {eng},
   issn = {0739-1102},
   journal = {Journal of Biomolecular Structure and Dynamics},
   title = {Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation},
   url = {http://www.tandfonline.com/doi/full/10.1080/07391102.2013.789401#.UoYzdScXeSk},
   volume = {32},
   year = {2014}
}

TY  - JOUR
ID  - 1129505
AU  - Ponomareva, Alla - Yurenko, Yevgen - Zhurakivsky, Roman - van Mourik, Tanja - Hovorun, Dmytro
PY  - 2014
TI  - Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation
JF  - Journal of Biomolecular Structure and Dynamics
VL  - 32
IS  - 5
SP  - 730-740
EP  - 730-740
PB  - Taylor & Francis
SN  - 07391102
KW  - 2 ' 3 ' -didehydro-2' 3 ' -dideoxyadenosine
KW  - 2 ' 3 ' -didehydro-2 ' 3 ' -dideoxyguanosine
KW  - d4A
KW  - d4G
KW  - conformational analysis
KW  - hydrogen bonds
KW  - H-bonds
KW  - biological activity
KW  - nucleoside reverse transcriptase inhibitors
KW  - density functional theory
UR  - http://www.tandfonline.com/doi/full/10.1080/07391102.2013.789401#.UoYzdScXeSk
L2  - http://www.tandfonline.com/doi/full/10.1080/07391102.2013.789401#.UoYzdScXeSk
N2  - A comprehensive quantum-chemical investigation of the conformational landscapes of two nucleoside HIV-1 reverse transcriptase inhibitors, d4A and d4G, has been performed. Both nucleosides are shaped by a sophisticated network of specific noncovalent interactions, including conventional OH_O, NH_O and weak CH_O, CH_N hydrogen bonds, as well as dihydrogen CH_HC contacts. For the OH_O, NH_O, and CH_O hydrogen bonds, natural bond orbital analysis revealed hyperconjugative interactions between the oxygen lone pairs and the antibonding orbital of the donor group. For the CH _HC contacts, the electron density migrates from the antibonding orbital, corresponding to the CH group of the sugar residue, to the bonding orbital relative to the same group in the nucleobase. The results confirm the current belief that the biological activity of d4A and d4G is connected with the termination of the DNA chain synthesis. Thus, these nucleosides act as competitive HIV-1 reverse transcriptase inhibitors.
ER  -

PONOMAREVA, Alla, Yevgen YURENKO, Roman ZHURAKIVSKY, Tanja VAN MOURIK and Dmytro HOVORUN. Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation. \textit{Journal of Biomolecular Structure and Dynamics}. Philadelphia: Taylor \&{} Francis, 2014, vol.~32, No~5, p.~730-740. ISSN~0739-1102. Available from: https://dx.doi.org/10.1080/07391102.2013.789401.

Detailed Information on Publication Record