Role of Pseudoisocytidine Tautomerization in Triplex-Forming Oligonucleotides: In Silico and in Vitro Studies

Yossa Dwi Hartono, Y. Vladimir Pabon-Martinez, Arzu Uyar, Jesper Wengel, Karin E. Lundin, Rula Zain, C. I.Edvard Smith, Lennart Nilsson, Alessandra Villa*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

221 Downloads (Pure)

Resumé

Pseudoisocytidine (1C) is a synthetic cytidine analogue that can target DNA duplex to form parallel triplex at neutral pH. Pseudoisocytidine has mainly two tautomers, of which only one is favorable for triplex formation. In this study, we investigated the effect of sequence on ψC tautomerization using -dynamics simulation, which takes into account transitions between states. We also performed in vitro binding experiments with sequences containing ψC and furthermore characterized the structure of the formed triplex using molecular dynamics simulation. We found that the neighboring methylated or protonated cytidine promotes the formation of the favorable tautomer, whereas the neighboring thymine or locked nucleic acid has a poor effect, and consecutive ψC has a negative influence. The deleterious effect of consecutive ψC in a triplex formation was confirmed using in vitro binding experiments. Our findings contribute to improving the design of ψC-containing triplex-forming oligonucleotides directed to target G-rich DNA sequences.

OriginalsprogEngelsk
TidsskriftACS Omega
Vol/bind2
Udgave nummer5
Sider (fra-til)2165-2177
Antal sider13
ISSN2470-1343
DOI
StatusUdgivet - 2017

Fingeraftryk

Cytidine
Oligonucleotides
Thymine
DNA sequences
Nucleic acids
Computer simulation
Molecular dynamics
DNA
Experiments
pseudoisocytidine
locked nucleic acid

Citer dette

Hartono, Y. D., Pabon-Martinez, Y. V., Uyar, A., Wengel, J., Lundin, K. E., Zain, R., ... Villa, A. (2017). Role of Pseudoisocytidine Tautomerization in Triplex-Forming Oligonucleotides: In Silico and in Vitro Studies. ACS Omega, 2(5), 2165-2177. https://doi.org/10.1021/acsomega.7b00347
Hartono, Yossa Dwi ; Pabon-Martinez, Y. Vladimir ; Uyar, Arzu ; Wengel, Jesper ; Lundin, Karin E. ; Zain, Rula ; Smith, C. I.Edvard ; Nilsson, Lennart ; Villa, Alessandra. / Role of Pseudoisocytidine Tautomerization in Triplex-Forming Oligonucleotides : In Silico and in Vitro Studies. I: ACS Omega. 2017 ; Bind 2, Nr. 5. s. 2165-2177.
@article{7a8dc04590624d70ad6d4aba3dddb133,
title = "Role of Pseudoisocytidine Tautomerization in Triplex-Forming Oligonucleotides: In Silico and in Vitro Studies",
abstract = "Pseudoisocytidine (1C) is a synthetic cytidine analogue that can target DNA duplex to form parallel triplex at neutral pH. Pseudoisocytidine has mainly two tautomers, of which only one is favorable for triplex formation. In this study, we investigated the effect of sequence on ψC tautomerization using -dynamics simulation, which takes into account transitions between states. We also performed in vitro binding experiments with sequences containing ψC and furthermore characterized the structure of the formed triplex using molecular dynamics simulation. We found that the neighboring methylated or protonated cytidine promotes the formation of the favorable tautomer, whereas the neighboring thymine or locked nucleic acid has a poor effect, and consecutive ψC has a negative influence. The deleterious effect of consecutive ψC in a triplex formation was confirmed using in vitro binding experiments. Our findings contribute to improving the design of ψC-containing triplex-forming oligonucleotides directed to target G-rich DNA sequences.",
author = "Hartono, {Yossa Dwi} and Pabon-Martinez, {Y. Vladimir} and Arzu Uyar and Jesper Wengel and Lundin, {Karin E.} and Rula Zain and Smith, {C. I.Edvard} and Lennart Nilsson and Alessandra Villa",
year = "2017",
doi = "10.1021/acsomega.7b00347",
language = "English",
volume = "2",
pages = "2165--2177",
journal = "ACS Omega",
issn = "2470-1343",
publisher = "ACS Publications",
number = "5",

}

Hartono, YD, Pabon-Martinez, YV, Uyar, A, Wengel, J, Lundin, KE, Zain, R, Smith, CIE, Nilsson, L & Villa, A 2017, 'Role of Pseudoisocytidine Tautomerization in Triplex-Forming Oligonucleotides: In Silico and in Vitro Studies', ACS Omega, bind 2, nr. 5, s. 2165-2177. https://doi.org/10.1021/acsomega.7b00347

Role of Pseudoisocytidine Tautomerization in Triplex-Forming Oligonucleotides : In Silico and in Vitro Studies. / Hartono, Yossa Dwi; Pabon-Martinez, Y. Vladimir; Uyar, Arzu; Wengel, Jesper; Lundin, Karin E.; Zain, Rula; Smith, C. I.Edvard; Nilsson, Lennart; Villa, Alessandra.

I: ACS Omega, Bind 2, Nr. 5, 2017, s. 2165-2177.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Role of Pseudoisocytidine Tautomerization in Triplex-Forming Oligonucleotides

T2 - In Silico and in Vitro Studies

AU - Hartono, Yossa Dwi

AU - Pabon-Martinez, Y. Vladimir

AU - Uyar, Arzu

AU - Wengel, Jesper

AU - Lundin, Karin E.

AU - Zain, Rula

AU - Smith, C. I.Edvard

AU - Nilsson, Lennart

AU - Villa, Alessandra

PY - 2017

Y1 - 2017

N2 - Pseudoisocytidine (1C) is a synthetic cytidine analogue that can target DNA duplex to form parallel triplex at neutral pH. Pseudoisocytidine has mainly two tautomers, of which only one is favorable for triplex formation. In this study, we investigated the effect of sequence on ψC tautomerization using -dynamics simulation, which takes into account transitions between states. We also performed in vitro binding experiments with sequences containing ψC and furthermore characterized the structure of the formed triplex using molecular dynamics simulation. We found that the neighboring methylated or protonated cytidine promotes the formation of the favorable tautomer, whereas the neighboring thymine or locked nucleic acid has a poor effect, and consecutive ψC has a negative influence. The deleterious effect of consecutive ψC in a triplex formation was confirmed using in vitro binding experiments. Our findings contribute to improving the design of ψC-containing triplex-forming oligonucleotides directed to target G-rich DNA sequences.

AB - Pseudoisocytidine (1C) is a synthetic cytidine analogue that can target DNA duplex to form parallel triplex at neutral pH. Pseudoisocytidine has mainly two tautomers, of which only one is favorable for triplex formation. In this study, we investigated the effect of sequence on ψC tautomerization using -dynamics simulation, which takes into account transitions between states. We also performed in vitro binding experiments with sequences containing ψC and furthermore characterized the structure of the formed triplex using molecular dynamics simulation. We found that the neighboring methylated or protonated cytidine promotes the formation of the favorable tautomer, whereas the neighboring thymine or locked nucleic acid has a poor effect, and consecutive ψC has a negative influence. The deleterious effect of consecutive ψC in a triplex formation was confirmed using in vitro binding experiments. Our findings contribute to improving the design of ψC-containing triplex-forming oligonucleotides directed to target G-rich DNA sequences.

U2 - 10.1021/acsomega.7b00347

DO - 10.1021/acsomega.7b00347

M3 - Journal article

C2 - 30023656

AN - SCOPUS:85028954692

VL - 2

SP - 2165

EP - 2177

JO - ACS Omega

JF - ACS Omega

SN - 2470-1343

IS - 5

ER -