Cyclopenta[f]isoquinoline derivatives designed to bind specifically to native deoxyribonucleic acid. III. Interaction of 6-carbamylmethyl-8-methyl-7 [formula omitted]-cyclopenta[f]isoquinolin-3(2 [formula omitted])-one with deoxyribonucleic acids and polydeoxyribonucleotides

Abstract

By the use of space-filling models, a novel compound, 6-carbamylmethyl-8-methyl-7 H -cyclopenta[f]isoquinolin-3(2 H )-one ( 1 ) was devised which would be expected to hydrogen bond specifically to GC pairs in the major groove of the double helix such that (i) the amino group of the cytosine molecule donates a hydrogen bond to the C-3 carbonyl of the isoquinoline moiety and (ii) the amide proton of the side chain donates a hydrogen bond to the N-7 of guanine. From difference spectra studies it was found that 1 binds to native calf thymus DNA better than to denatured DNA; 1 inhibited RNA synthesis by a DNA-dependent RNA polymerase; and equilibrium dialysis experiments revealed that 1 binds to poly(dG).poly(dC), whereas no such binding to poly(dA).poly(dT) was observed.