Acridine derivatives are known for their affinity for DNA and their intercalating properties. The idea of combining the DNA binding properties of acridines with the geometry and chirality of Tröger's Base was very attractive to design a new family of chiral DNA binding molecules. The geometry of the Tröger's Base unit gives the molecules an helix shape that can be compared to the helicity of DNA as shown below.

3D modelisation

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Since the work of Watson and Crick describing DNA as a right-handed helix or B-conformation, x-ray studies of synthetic oligonucleotides have shown that other conformations were also possible and among them, a left-handed or Z-conformation. The existence in vivo and the biological role of this Z-conformation is still unclear. The development of molecular probes to study local conformations in DNA is of major interest and until now, only chiral metal complexes have been shown to achieve enantioselective recognition of DNA conformations. The possibility that acridine analogue of Tröger's Bases could achieve chiral discrimination of DNA conformations was subjected to a preliminary molecular modeling study.


The interaction of the two isomers of the unsubstituted acridine analogue of Tröger's Base TB with short oligonucleotides was calculated. Two binding modes were analyzed, the first one corresponding to the intercalation of one acridine unit the other lying in a groove, and the second one involving docking of the two acridine units in the same groove. In the two schemes, the calculations clearly showed enantioselectivity in the binding, with variations depending on the mode of complexation and on the DNA sequences.

Molecular modelling approach

(R,R) and (S,S) enantiomers interact with DNA both by intercalation and by groove binding in different modes. Two examples are presented here.

1) One acridine ring is intercalated between adjacent base pairs, the other acridine being set in the minor or major groove.
Intercalation with minor groove interaction is shown below:

2) The second mode involves binding of both acridine moieties in a groove.
Major groove interaction is shown below:

Molecular modelling predicts a selective recognition of Tröger's Base enantiomers by DNA.
The enantioselectivity depends on the modes of binding and on the DNA sequences.

Ref. : Y. Coppel, Ce. Coulombeau, C. Coulombeau, J. Lhomme, M. L. Dheu-Andries, P. Vatton
J. Biomol. Struct. Dyn., 1994, Vol. 12, 637.

[Summary] [Synthesis] [Physico...] [Interaction...] [Enantioselective...] [Conclusion]