A theoretical study of anthracene and phenanthrene derivatives acting as A-T specific intercalators.
Theoretical computations are performed on the comparative A-T versus G-C binding selectivities of two DNA intercalating molecules recently synthesized by Wilson et al. These are derivatives of phenanthrene and anthracene with side chains containing an hydroxy group bound to its C alpha carbon and a cationic amino group bound to its C beta carbon. We have optimized the binding energies of these phenanthrene and anthracene derivatives (1 and 2, respectively) to the double-stranded tetramers d(ATAT)2 and d(GCGC)2, the intercalation occurring in the central pyrimidine (3'-5') purine sequence. The sum of the intercalator-oligonucleotide intermolecular interaction energy plus the conformational energy variation of the intercalator upon binding were computed by the SIBFA procedures, which use empirical formulas based on ab initio SCF computations. Both compounds are found to bind more favourably to the AT sequence than to the GC one. Moreover, the affinity of 1 for the AT oligomer is computed to be larger than that of 2, whereas conversely that of 2 is larger than that of 1 for the GC oligomer. The AT versus GC binding selectivity of 1 is significantly larger than that of 2. These results are in excellent agreement with the experimental findings of Wilson et al. However, contrary to the suggestion of these authors the alpha-hydroxy group of the side chain of the intercalators does not seem to play a decisive role in determining the A-T specificity.
D000225:Adenine; D000873:Anthracenes; D001482:Base Composition; D003596:Cytosine; D004247:DNA; D006151:Guanosine; D007364:Intercalating Agents; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010616:Phenanthrenes; D013329:Structure-Activity Relationship; D013941:Thymine
D000873:Anthracenes; D007364:Intercalating Agents; D010616:Phenanthrenes; D006151:Guanosine; D003596:Cytosine; D004247:DNA; D000225:Adenine; D013941:Thymine