title: Hoogsteen DNA duplexes of 3'-3'- and 5'-5'-linked oligonucleotides and trip formation with RNA and DNA pyrimidine single strands: experimental and molecular modeling studies.
abstract: DNA oligonucleotide sequences containing two parallel complementary strands attached through 3'-3' and 5'-5' linkages were synthesized. These oligonucleotides from Hoogsteen base-paired parallel-stranded (PS) hairpin duplexes under appropriate conditions [Kandimalla, E. R., Agrawal, S., Venkataraman, G., & Sasisekharan, V. (1995a) J. Am. Chem. Soc. 117, 6416-6417]. UV melting experiments show that these Hoogsteen hairpin duplexes have a lower thermal stability than that of the Watson-Crick (WC) hairpin duplex (antiparallel) of the same sequence. The circular dichroism (CD) spectrum of the Hoogsteen duplex is different from the canonical B-DNA WC duplex spectrum. The formation of the Hoogsteen duplex is pH-dependent since protonation of cytosine requires lower pH conditions. Studies with oligonucleotides of different loop sizes revel that three- and two-base loops are optimum for the formation of stable Hoogsteen duplexes with 3'-3' and 5'-5' linkages, respectively. The guanine residues in the loop stabilize the duplex as a result of G-G interactions as confirmed by molecular modeling studies. The new PS Hoogsteen duplexes form stable triplexes with complementary (antiparallel to the purine domain) single-stranded RNA and DNA pyrimidine sequences in Py.Pu:Py (pyrimidine third strand-purine WC strand:pyrimidine WC strand) motif. The thermal stability of the resulting triplexes is much higher than that of the conventional triplex (binding of a Hoogsteen pyrimidine third strand to a WC duplex) of the same sequence. The CD spectra of the new triplexes are similar to those of conventional triplexes, suggesting that no conformational change occurs as a result of 3'-3' or 5'-5' linkage. A molecular modeling study was carried out to examine the stereochemical feasibility of the Hoogsteen duplexes and formation of triplexes with single-stranded pyrimidine complementary strands.
authors.affiliation: Hybridon, Inc., Worcester, Massachusetts 01605, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Kandimalla
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; D011743:Pyrimidines; D012313:RNA; D004247:DNA