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Structural and Energetic Impact of Non‐natural 7‐Deaza‐8‐azaguanine, 7‐Deaza‐8‐azaisoguanine, and Their 7‐Substituted Derivatives on Hydrogen‐Bond Pairing with Cytosine and Isocytosine
Author(s) -
Chawla Mohit,
Minenkov Yury,
Vu Khanh B.,
Oliva Romina,
Cavallo Luigi
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900245
Subject(s) - substituent , chemistry , base pair , stereochemistry , crystallography , molecular structure of nucleic acids: a structure for deoxyribose nucleic acid , cytosine , hydrogen bond , computational chemistry , molecule , dna , organic chemistry , biochemistry
The impact of 7‐deaza‐8‐azaguanine (DAG) and 7‐deaza‐8‐azaisoguanine (DAiG) modifications on the geometry and stability of the G:C Watson–Crick (cWW) base pair and the G:iC and iG:C reverse Watson–Crick (tWW) base pairs has been characterized theoretically. In addition, the effect on the same base pairs of seven C7‐substituted DAG and DAiG derivatives, some of which have been previously experimentally characterized, has been investigated. Calculations indicate that all of these modifications have a negligible impact on the geometry of the above base pairs, and that modification of the heterocycle skeleton has a 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, a linear correlation between the base‐pair interaction energy and the Hammett constant of the 7‐substituent is found, 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.