Synthesis of novel DNA binding agents: indole-containing analogues of bis-netropsin

Molecular modelling studies showed that indole dicarboxylic acids are poten tial linkers for the synthesis of bis-netropsin analogues with a good fit t o the minor groove of DNA. To test this hypothesis, 2-carboxyindole-6-aceti c acid, indole-2,6-dicarboxylic acid, 6-(2-carboxyethyl)indole-2-carboxylic acid, 6-(2-carboxy-1-ethenyl)indole-2-carboxylic acid were prepared and co upled to 3-[1-methyl-4-(1-methyl-4-aminopyrrole-2-carboxamido)pyrrole-2-car boxamido]dimethylaminopropane. Similarly indole-2,5-dicarboxylic acid was p repared and coupled to 3-[1-methyl-4-(1-methyl-4-aminopyrrple-2-carboxamido )pyrrole-2-carboxamido]propionamidine hydrochloride. The. The derivatives o f 26-28 showed especially strong binding to AT rich regions as shown by foo tprinting studies.