Open AccessNucleic acid duplexes incorporating a dissociable covalent base pair
Author(s) -
Kui Gao,
Leslie E. Orgel
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.26.14837
Subject(s) - nucleic acid , covalent bond , oligonucleotide , base pair , chemistry , duplex (building) , nucleic acid structure , nucleic acid analogue , nucleic acid thermodynamics , dna , base (topology) , stereochemistry , combinatorial chemistry , biochemistry , rna , base sequence , organic chemistry , mathematical analysis , mathematics , gene
We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure.