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.
abstract: Non-natural (synthetic) nucleobases, including 7-ethynyl- and 7-triazolyl-8-aza-7-deazaadenine, 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 adenine skeleton, and we moved then to analyze the impact of the specific substituents on the modified 8-aza-7-deazaadenine. 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 guanine when paired to cytosine. To stress further the H-bonding pairing in the modified adenine-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.
authors.affiliation: Physical Sciences and Engineering Division, Kaust Catalysis Center, King Abdullah University of Science and Technology (KAUST) , Thuwal 23955-6900, Saudi Arabia.
authors.forename: Mohit
authors.initials: M
authors.lastname: Chawla
authors.affiliation: Physical Sciences and Engineering Division, Kaust Catalysis Center, King Abdullah University of Science and Technology (KAUST) , Thuwal 23955-6900, Saudi Arabia.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Credendino
authors.affiliation: Department of Sciences and Technologies, University Parthenope of Naples , Centro Direzionale Isola C4, I-80143, Naples, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Oliva
authors.affiliation: Physical Sciences and Engineering Division, Kaust Catalysis Center, King Abdullah University of Science and Technology (KAUST) , Thuwal 23955-6900, Saudi Arabia.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavallo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D006860:Hydrogen Bonding; D015394:Molecular Structure; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics; D014498:Uracil / Q000737:chemistry*
chemical_list: C414764:8-aza-7-deazaadenine; D014498:Uracil; D012313:RNA; D000225:Adenine