Antiparallel triple helices. Structural characteristics and stabilization by 8-amino derivatives.

TitleAntiparallel triple helices. Structural characteristics and stabilization by 8-amino derivatives.
Publication TypeJournal Article
Year of Publication2003
AuthorsAviñó, Anna, Cubero Elena, González Carlos, Eritja Ramon, and Orozco Modesto
JournalJ Am Chem Soc
Date Published2003 Dec 24
KeywordsAmines, Biomolecular, Computer Simulation, DNA, Guanine, Models, Molecular, Nuclear Magnetic Resonance, Nucleic Acid Conformation, Oligonucleotides, Purines, Thermodynamics

The structural, dynamical, and recognition properties of antiparallel DNA triplexes formed by the antiparallel d(G#G.C), d(A#A.T), and d(T#A.T) motifs (the pound sign and dot mean reverse-Hoogsteen and Watson-Crick hydrogen bonds, respectively) are studied by means of "state of the art" molecular dynamics simulations. Once the characteristics of the helix are defined, molecular dynamics and thermodynamic integration calculations are used to determine the expected stabilization of the antiparallel triplex caused by the introduction of 8-aminopurines. Finally, oligonucleotides containing 8-aminopurine derivatives are synthesized and tested experimentally using several approaches in a variety of systems. A very large stabilization of the triplex is found experimentally, as predicted by simulations. These results open the possibility for the use of oligonucleotides carrying 8-aminopurines to bind single-stranded nucleic acids by formation of antiparallel triplexes.