Cargando…

Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog

A truly universal nucleobase enables a host of novel applications such as simplified templates for PCR primers, randomized sequencing and DNA based devices. A universal base must pair indiscriminately to each of the canonical bases with little or preferably no destabilization of the overall duplex....

Descripción completa

Detalles Bibliográficos
Autores principales: Spring-Connell, Alexander M., Evich, Marina G., Debelak, Harald, Seela, Frank, Germann, Markus W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062995/
https://www.ncbi.nlm.nih.gov/pubmed/27566150
http://dx.doi.org/10.1093/nar/gkw736
_version_ 1782459892209025024
author Spring-Connell, Alexander M.
Evich, Marina G.
Debelak, Harald
Seela, Frank
Germann, Markus W.
author_facet Spring-Connell, Alexander M.
Evich, Marina G.
Debelak, Harald
Seela, Frank
Germann, Markus W.
author_sort Spring-Connell, Alexander M.
collection PubMed
description A truly universal nucleobase enables a host of novel applications such as simplified templates for PCR primers, randomized sequencing and DNA based devices. A universal base must pair indiscriminately to each of the canonical bases with little or preferably no destabilization of the overall duplex. In reality, many candidates either destabilize the duplex or do not base pair indiscriminatingly. The novel base 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin- 4-amine) N(8)-(2′deoxyribonucleoside), a deoxyadenosine analog (UB), pairs with each of the natural DNA bases with little sequence preference. We have utilized NMR complemented with molecular dynamic calculations to characterize the structure and dynamics of a UB incorporated into a DNA duplex. The UB participates in base stacking with little to no perturbation of the local structure yet forms an unusual base pair that samples multiple conformations. These local dynamics result in the complete disappearance of a single UB proton resonance under native conditions. Accommodation of the UB is additionally stabilized via heightened backbone conformational sampling. NMR combined with various computational techniques has allowed for a comprehensive characterization of both structural and dynamic effects of the UB in a DNA duplex and underlines that the UB as a strong candidate for universal base applications.
format Online
Article
Text
id pubmed-5062995
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-50629952016-10-14 Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog Spring-Connell, Alexander M. Evich, Marina G. Debelak, Harald Seela, Frank Germann, Markus W. Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry A truly universal nucleobase enables a host of novel applications such as simplified templates for PCR primers, randomized sequencing and DNA based devices. A universal base must pair indiscriminately to each of the canonical bases with little or preferably no destabilization of the overall duplex. In reality, many candidates either destabilize the duplex or do not base pair indiscriminatingly. The novel base 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin- 4-amine) N(8)-(2′deoxyribonucleoside), a deoxyadenosine analog (UB), pairs with each of the natural DNA bases with little sequence preference. We have utilized NMR complemented with molecular dynamic calculations to characterize the structure and dynamics of a UB incorporated into a DNA duplex. The UB participates in base stacking with little to no perturbation of the local structure yet forms an unusual base pair that samples multiple conformations. These local dynamics result in the complete disappearance of a single UB proton resonance under native conditions. Accommodation of the UB is additionally stabilized via heightened backbone conformational sampling. NMR combined with various computational techniques has allowed for a comprehensive characterization of both structural and dynamic effects of the UB in a DNA duplex and underlines that the UB as a strong candidate for universal base applications. Oxford University Press 2016-10-14 2016-08-26 /pmc/articles/PMC5062995/ /pubmed/27566150 http://dx.doi.org/10.1093/nar/gkw736 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Chemical Biology and Nucleic Acid Chemistry
Spring-Connell, Alexander M.
Evich, Marina G.
Debelak, Harald
Seela, Frank
Germann, Markus W.
Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog
title Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog
title_full Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog
title_fullStr Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog
title_full_unstemmed Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog
title_short Using NMR and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, N8 linked adenosine analog
title_sort using nmr and molecular dynamics to link structure and dynamics effects of the universal base 8-aza, 7-deaza, n8 linked adenosine analog
topic Chemical Biology and Nucleic Acid Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062995/
https://www.ncbi.nlm.nih.gov/pubmed/27566150
http://dx.doi.org/10.1093/nar/gkw736
work_keys_str_mv AT springconnellalexanderm usingnmrandmoleculardynamicstolinkstructureanddynamicseffectsoftheuniversalbase8aza7deazan8linkedadenosineanalog
AT evichmarinag usingnmrandmoleculardynamicstolinkstructureanddynamicseffectsoftheuniversalbase8aza7deazan8linkedadenosineanalog
AT debelakharald usingnmrandmoleculardynamicstolinkstructureanddynamicseffectsoftheuniversalbase8aza7deazan8linkedadenosineanalog
AT seelafrank usingnmrandmoleculardynamicstolinkstructureanddynamicseffectsoftheuniversalbase8aza7deazan8linkedadenosineanalog
AT germannmarkusw usingnmrandmoleculardynamicstolinkstructureanddynamicseffectsoftheuniversalbase8aza7deazan8linkedadenosineanalog