Rational design of a triple helix-specific intercalating ligand.

Abstract:

:DNA triple helices offer new perspectives toward oligonucleotide-directed gene regulation. However, the poor stability of some of these structures might limit their use under physiological conditions. Specific ligands can intercalate into DNA triple helices and stabilize them. Molecular modeling and thermal denaturation experiments suggest that benzo[f]pyrido[3, 4-b]quinoxaline derivatives intercalate into triple helices by stacking preferentially with the Hoogsteen-paired bases. Based on this model, it was predicted that a benzo[f]quino[3,4-b]quinoxaline derivative, which possesses an additional aromatic ring, could engage additional stacking interactions with the pyrimidine strand of the Watson-Crick double helix upon binding of this pentacyclic ligand to a triplex structure. This compound was synthesized. Thermal denaturation experiments and inhibition of restriction enzyme cleavage show that this new compound can indeed stabilize triple helices with great efficiency and specificity and/or induce triple helix formation under physiological conditions.

authors

Escudé C,Nguyen CH,Kukreti S,Janin Y,Sun JS,Bisagni E,Garestier T,Hélène C

doi

10.1073/pnas.95.7.3591

subject

Has Abstract

pub_date

1998-03-31 00:00:00

pages

3591-6

issue

7

eissn

0027-8424

issn

1091-6490

journal_volume

95

pub_type

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