title: Single-stranded DNA and RNA targeted triplex-formation: UV, CD and molecular modeling studies of foldback triplexes containing different RNA, 2'-OMe-RNA and DNA strand combinations.
abstract: We studied the influence of different 2'-OMe-RNA and DNA strand combinations on single strand targeted foldback triplex formation in the Py.Pu:Py motif using ultraviolet (UV) and circular dichroism (CD) spectroscopy, and molecular modeling. The study of eight combinations of triplexes (D.D:D, R*.D:D, D.D:R*, R*.D:R*, D.R:D, R*.R:D, D.R:R*, and R*.R:R*; where the first, middle, and last letters stand for the Hoogsteen Pyrimidine, Watson-Crick [WC] purine and WC pyrimidine strands, respectively, and D, R and R* stand for DNA, RNA and 2'-OMe-RNA strands, respectively) indicate more stable foldback triplex formation with a DNA purine strand than with an RNA purine strand. Of the four possible WC duplexes with RNA/DNA combinations, the duplex with a DNA purine strand and a 2'-O-Me-RNA pyrimidine strand forms the most thermally stable triplex, although its thermal stability is the lowest of all four duplexes. Irrespective of the duplex combination, a 2'-OMe-RNA Hoogsteen pyrimidine strand forms a stable foldback triplex over a DNA Hoogsteen pyrimidine strand confirming the earlier reports with conventional and circular triplexes. The CD studies suggest a B-type conformation for an all DNA homo-foldback triplex (D.D:D), while hetero-foldback triplex spectra suggest intermediate conformation to both A-type and B-type structures. A novel molecular modeling study has been carried out to understand the stereochemical feasibility of all the combinations of foldback triplexes using a geometric approach. The new approach allows use of different combinations of chain geometries depending on the nature of the chain (RNA vs. DNA).
authors.affiliation: Hybridon, Inc., Cambridge, MA, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Kandimalla
authors.forename: G
authors.initials: G
authors.lastname: Venkataraman
authors.forename: V
authors.initials: V
authors.lastname: Sasisekharan
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D002942:Circular Dichroism; D004277:DNA, Single-Stranded / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D014466:Ultraviolet Rays
chemical_list: D004277:DNA, Single-Stranded; D012313:RNA