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Nucleic Acids Research, Vol 26, Issue 9 2179-2183, Copyright © 1998 by Oxford University Press


ARTICLES

Triple helices formed at oligopyrimidine*oligopurine sequences with base pair inversions: effect of a triplex-specific ligand on stability and selectivity

S Kukreti, JS Sun, D Loakes, DM Brown, CH Nguyen, E Bisagni, T Garestier and C Helene
Laboratoire de Biophysique, Museum National d'Histoire Naturelle, INSERM U201, CNRS URA481, 43 rue Cuvier, 75231 Paris Cedex 05, France.

Oligonucleotide-directed triple helix formation is mostly restricted to oligopyrimidine*oligopurine sequences of double helical DNA. An interruption of one or two pyrimidines in the oligopurine target strand leads to a strong triplex destabilisation. We have investigated the effect of nucleotide analogues introduced in the third strand at the site opposite the base pair inversion(s). We show that a 3-nitropyrrole derivative (M) discriminates G*C from C*G, A*T and T*A in the presence of a triplex-specific ligand (a benzo[e]pyridoindole derivative, BePI). N6-methoxy-2,6-diaminopurine (K) binds to an A*T base pair better than a T*A, G*C or C*G base pair. Some discrimination is still observed in the presence of BePI and triplex stability is markedly increased. These findings should help in designing BePI-oligonucleotide conjugates to extend the range of DNA sequences available for triplex formation.
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