NOVEL HOOGSTEEN-LIKE BASES FOR RECOGNITION OF THE C-G BASE-PAIR BY DNA TRIPLEX FORMATION

Effective sequence-specific recognition of duplex DNA is possible by t ripler formation with natural oligonucleotides via Hoogsteen H-bonding . However, tripler formation is in practice limited to pyrimidine olig onucleotides that bind duplex A-T or G-C base pair DNA sequences speci fically at homopurine sites in the major groove as T . A-T and C+. G-C triplets. Here we report the successful modelling of novel unnatural nucleosides that recognize the C-G DNA base pair by Hoogsteen-like maj or groove interaction. These novel Hoogsteen nucleotides are examined within model A-type and B-type conformation tripler structures since t he DNA tripler can be considered to incorporate A-type and/or B-type c onfigurational properties. Using the same deoxyribose-phosphodiester a nd base-deoxyribose dihedral angle configuration, a triplet comprised of a C-G base pair and the novel Hoogsteen nucleotide, Y2, replaces th e central T . A-T tripler in the tripler. The presence of any structur al or energetic perturbations due to the central triplet in the energy -minimized tripler is assessed with respect to the unmodified energy m inimized (T . A-T)(11) starting structures. Incorporation of this nove l triplet into both A-type and B-type natural tripler structures provo kes minimal change in the configuration of the central and adjacent tr iplets.