Structural and Energetic Impact of Non-Natural 7-Deaza-8-Azaadenine and its 7-Substituted Derivatives on H-Bonding Potential with Uracil in RNA Molecules

Handle URI:
http://hdl.handle.net/10754/578843
Title:
Structural and Energetic Impact of Non-Natural 7-Deaza-8-Azaadenine and its 7-Substituted Derivatives on H-Bonding Potential with Uracil in RNA Molecules
Authors:
Chawla, Mohit; Credendino, Raffaele; Oliva, Romina; Cavallo, Luigi ( 0000-0002-1398-338X )
Abstract:
Non-natural (synthetic) nucleobases, including 7-ethynyl- and 7-triazolyl-8-aza-7-deazaadenosine, have been introduced in RNA molecules for targeted applications, and have been characterized experimentally. However, no theoretical characterization of the impact of these modifications on the structure and energetics of the corresponding H-bonded base pair is available. To fill this gap, we performed quantum mechanics calculations, starting with the analysis of the impact of the 8-aza-7-deaza modification of the adenosine skeleton, and we moved then to analyze the impact of the specific substituents on the modified 8-aza-7-deazaadenosine. Our analysis indicates that, despite of these severe structural modifications, the H-bonding properties of the modified base pair gratifyingly replicate those of the unmodified base pair. Similar behavior is predicted when the same skeleton modifications are applied to guanosine when paired to cytosine. To stress further the H-bonding pairing in the modified adenosine-uracil base pair, we explored the impact of strong electron donor and electron withdrawing substituents on the C7 position. Also in this case we found minimal impact on the base pair geometry and energy, confirming the validity of this modification strategy to functionalize RNAs without perturbing its stability and biological functionality.
KAUST Department:
Physical Sciences and Engineering (PSE) Division; KAUST Catalysis Center (KCC)
Citation:
Structural and Energetic Impact of Non-Natural 7-Deaza-8-Azaadenine and its 7-Substituted Derivatives on H-Bonding Potential with Uracil in RNA Molecules 2015:150921112823007 The Journal of Physical Chemistry B
Publisher:
American Chemical Society (ACS)
Journal:
The Journal of Physical Chemistry B
Issue Date:
21-Sep-2015
DOI:
10.1021/acs.jpcb.5b06861
Type:
Article
ISSN:
1520-6106; 1520-5207
Additional Links:
http://pubs.acs.org/doi/10.1021/acs.jpcb.5b06861
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; KAUST Catalysis Center (KCC)

Full metadata record

DC FieldValue Language
dc.contributor.authorChawla, Mohiten
dc.contributor.authorCredendino, Raffaeleen
dc.contributor.authorOliva, Rominaen
dc.contributor.authorCavallo, Luigien
dc.date.accessioned2015-09-29T05:23:55Zen
dc.date.available2015-09-29T05:23:55Zen
dc.date.issued2015-09-21en
dc.identifier.citationStructural and Energetic Impact of Non-Natural 7-Deaza-8-Azaadenine and its 7-Substituted Derivatives on H-Bonding Potential with Uracil in RNA Molecules 2015:150921112823007 The Journal of Physical Chemistry Ben
dc.identifier.issn1520-6106en
dc.identifier.issn1520-5207en
dc.identifier.doi10.1021/acs.jpcb.5b06861en
dc.identifier.urihttp://hdl.handle.net/10754/578843en
dc.description.abstractNon-natural (synthetic) nucleobases, including 7-ethynyl- and 7-triazolyl-8-aza-7-deazaadenosine, have been introduced in RNA molecules for targeted applications, and have been characterized experimentally. However, no theoretical characterization of the impact of these modifications on the structure and energetics of the corresponding H-bonded base pair is available. To fill this gap, we performed quantum mechanics calculations, starting with the analysis of the impact of the 8-aza-7-deaza modification of the adenosine skeleton, and we moved then to analyze the impact of the specific substituents on the modified 8-aza-7-deazaadenosine. Our analysis indicates that, despite of these severe structural modifications, the H-bonding properties of the modified base pair gratifyingly replicate those of the unmodified base pair. Similar behavior is predicted when the same skeleton modifications are applied to guanosine when paired to cytosine. To stress further the H-bonding pairing in the modified adenosine-uracil base pair, we explored the impact of strong electron donor and electron withdrawing substituents on the C7 position. Also in this case we found minimal impact on the base pair geometry and energy, confirming the validity of this modification strategy to functionalize RNAs without perturbing its stability and biological functionality.en
dc.language.isoenen
dc.publisherAmerican Chemical Society (ACS)en
dc.relation.urlhttp://pubs.acs.org/doi/10.1021/acs.jpcb.5b06861en
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry B, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/10.1021/acs.jpcb.5b06861.en
dc.titleStructural and Energetic Impact of Non-Natural 7-Deaza-8-Azaadenine and its 7-Substituted Derivatives on H-Bonding Potential with Uracil in RNA Moleculesen
dc.typeArticleen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentKAUST Catalysis Center (KCC)en
dc.identifier.journalThe Journal of Physical Chemistry Ben
dc.eprint.versionPost-printen
dc.contributor.institutionDepartment of Sciences and Technologies, University Parthenope of Naples, Centro Direzionale Isola C4, I,80143, Naples, Italyen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorCredendino, Raffaeleen
kaust.authorCavallo, Luigien
kaust.authorChawla, Mohiten
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