Structural and Energetic Impact of Non-natural 7-Deaza-8-Azaguanine, 7-Deaza-8-Azaisoguanine and their 7-Substituted Derivatives on H-bonding Pairing with Cytosine and Isocytosine
KAUST DepartmentPhysical Sciences and Engineering (PSE) Division
Chemical Science Program
KAUST Catalysis Center (KCC)
Permanent link to this recordhttp://hdl.handle.net/10754/631946
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AbstractWe theoretically characterized the impact that the 7-deaza-8-azaguanine (DAG) and 7-deaza-8-azaisoguanine (DAiG) modifications have on the geometry and stability of the G:C Watson-Crick (cWW) base pair and of the G:iC and iG:C reverse Watson-Crick (tWW) base pairs. In addition, we investigated the effect on the same base pairs of seven C7-substituted DAG and DAiG, some of which have been previously experimentally characterized. Our calculations indicate that all these modifications have a negligible impact on the geometry of the above base pairs, and that the modification of the heterocycle skeleton has small impact on the base pair interaction energies. Instead, base pair interaction energies are dependent on the nature of the C7 substituent. For the 7-substituted DAG-C cWW systems we found a linear correlation between the base pair interaction energy and the Hammett constant of the 7-substituent, with higher interaction energies corresponding to more electron-withdrawing substituents. Therefore, the explored modifications are expected to be accommodated in both parallel and antiparallel nucleic acid duplexes without perturbing their geometry, while the strength of a base pair (and duplex) featuring a DAG modification can in principle be tuned by incorporating different substituents at the C7 position.
CitationChawla M, Minenkov Y, Vu KB, Oliva R, Cavallo L (2019) Structural and Energetic Impact of Non-natural 7-Deaza-8-Azaguanine, 7-Deaza-8-Azaisoguanine and their 7-Substituted Derivatives on H-bonding Pairing with Cytosine and Isocytosine. ChemBioChem. Available: http://dx.doi.org/10.1002/cbic.201900245.
SponsorsLC thanks the King Abdullah University of Science and Technology (KAUST) for financial support. For computer time, this research used the resources of the Supercomputing Laboratory at KAUST.