Structure and energetics in the complexes of a double-stranded B-DNA dodecamer with netropsin derivatives of a tricationic water-soluble porphyrin: a theoretical investigation.

The structural and energetical characteristics of the complexes formed between two auto-complementary DNA dodecamers, d(CGCGAATTCGCG)2, and d(GCGCAATTGCGC)2, and two novel netropsin (I) and glycine-netropsin (II) conjugates of a tricationic water-soluble porphyrin are investigated in detail by means of theoretical computations. This study was prompted by the successful chemical synthesis of II, which was recently reported (Anneheim-Herbelin, G., Perrée-Fauvet, M., Gaudemer, A., Hélissey, P., Giorgi-Renault, S. and Gresh, N., Tetrahedron Lett. 34, 7263 (1993)). The results indicate that: a) Intercalative binding of II does not entail significant distortions of the DNA backbone, and the Net moiety can bind tightly to the core of the minor groove. b) Intercalative binding of I is computed to energetically weaker than that of II. This is a consequence of the reduced length of the oligopeptide arm, such that the terminal propionamidinium group interacts less favorably with the fourth A-T base-pair than is the case with II. c) Nonintercalative binding of II produces considerable conformational distortions of the DNA. These results in a break of the DNA axis in between the fourth and the fifth base-pairs, namely, at the level where the long axis of the chromophore and of the oligopeptide intersect.