title: Proton NMR studies of 5'-d-(TC)(3) (CT)(3) (AG)(3)-3'--a paperclip triplex: the structural relevance of turns.
abstract: In this study, we present the results of structural analysis of an 18-mer DNA 5'-T(1)C(2)T(3)C(4)T(5)C(6)C(7)T(8)C(9)T(10)C(11)T(12)A(13)G(14)A(15)G(16)A(17)G(18)-3' by proton nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. The NMR data are consistent with characteristics for triple helical structures of DNA: downfield shifting of resonance signals, typical for the H3(+) resonances of Hoogsteen-paired cytosines; pH dependence of these H3(+) resonance; and observed nuclear Overhauser effects consistent with Hoogsteen and Watson-Crick basepairing. A three-dimensional model for the triplex is developed based on data obtained from two-dimensional NMR studies and molecular modeling. We find that this DNA forms an intramolecular "paperclip" pyrimidine-purine-pyrimidine triple helix. The central triads resemble typical Hoogsteen and Watson-Crick basepairing. The triads at each end region can be viewed as hairpin turns stabilized by a third base. One of these turns is comprised of a hairpin turn in the Watson-Crick basepairing portion of the 18-mer with the third base coming from the Hoogsteen pairing strand. The other turn is comprised of two bases from the continuous pyrimidine portion of the 18-mer, stabilized by a hydrogen-bond from a purine. This "triad" has well defined structure as indicated by the number of nuclear Overhauser effects and is shown to play a critical role in stabilizing triplex formation of the internal triads.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Pasternack
authors.forename: Shwu-Bin
authors.initials: SB
authors.lastname: Lin
authors.forename: Tsung-Mei
authors.initials: TM
authors.lastname: Chin
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Lin
authors.forename: Dee-Hua
authors.initials: DH
authors.lastname: Huang
authors.forename: Lou-Sing
authors.initials: LS
authors.lastname: Kan
mesh_terms: D001483:Base Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011522:Protons; D013056:Spectrophotometry, Ultraviolet
chemical_list: D009838:Oligodeoxyribonucleotides; D011522:Protons; D004247:DNA