Hoogsteen-based parallel-stranded duplexes of DNA. Effect of 8-amino-purine derivatives.

TitleHoogsteen-based parallel-stranded duplexes of DNA. Effect of 8-amino-purine derivatives.
Publication TypeJournal Article
Year of Publication2002
AuthorsCubero, Elena, Aviñó Anna, de la Torre Beatriz G., Frieden Miriam, Eritja Ramon, F Luque Javier, González Carlos, and Orozco Modesto
JournalJ Am Chem Soc
Date Published2002 Mar 27
KeywordsBiomolecular, Circular Dichroism, Computer Simulation, Dinucleoside Phosphates, DNA, Models, Molecular, Nuclear Magnetic Resonance, Nucleic Acid Conformation, Oligonucleotides, Polydeoxyribonucleotides, Purines, Thermodynamics

The structure of parallel-stranded duplexes of DNA-containing a mixture of guanines (G) and adenines (A) is studied by means of molecular dynamics (MD) simulation, as well as NMR and circular dichroism (CD) spectroscopy. Results demonstrate that the structure is based on the Hoogsteen motif rather than on the reverse Watson-Crick one. Molecular dynamics coupled to thermodynamic integration (MD/TI) calculations and melting experiments allowed us to determine the effect of 8-amino derivatives of A and G and of 8-amino-2’-deoxyinosine on the stability of parallel-stranded duplexes. The large stabilization of the parallel-stranded helix upon 8-amino substitution agrees with a Hoogsteen pairing, confirming MD, NMR, and CD data, and suggests new methods to obtain DNA triplexes for antigene and antisense purposes.