title: High fidelity of base pairing by 2-selenothymidine in DNA.
abstract: The base pairs are the contributors to the sequence-dependent recognition of nucleic acids, genetic information storage, and high fidelity of DNA polymerase replication. However, the wobble base pairing, where T pairs with G instead of A, reduces specific base-pairing recognition and compromises the high fidelity of the enzymatic polymerization. Via the selenium atomic probing at the 2-position of thymidine, we have investigated the wobble discrimination by manipulating the steric and electronic effects at the 2-exo position, providing a unique chemical strategy to enhance the base pair specificity. We report here the first synthesis of the novel 2-Se-thymidine ((Se)T) derivative, its phosphoramidite, and the Se-DNAs. Our biophysical and structural studies of the 2-Se-T DNAs reveal that the bulky 2-Se atom with a weak hydrogen-bonding ability can largely increase mismatch discriminations (including T/G wobble and T/C mismatched base pairs) while maintaining the (Se)T/A virtually identical to the native T/A base pair. The 2-Se atom bulkiness and the electronic effect are probably the main factors responsible for the discrimination against the formation of the wobble (Se)T/G base pair. Our investigations provide a potential novel tool to investigate the specific recognition of base pairs, which is the basis of high fidelity during replication, transcription, and translation. Furthermore, this Se-atom-specific substitution and probing are useful for X-ray crystal structure and function studies of nucleic acids.
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA.
authors.forename: Abdalla E A
authors.initials: AE
authors.lastname: Hassan
authors.forename: Jia
authors.initials: J
authors.lastname: Sheng
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D016566:Organoselenium Compounds / Q000737:chemistry*; D013379:Substrate Specificity; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C549085:2-selenothymidine; D009943:Organophosphorus Compounds; D016566:Organoselenium Compounds; C434331:phosphoramidite; D004247:DNA; D013936:Thymidine