A series of monocationic lexitropsins, or information-reading oligopeptides, were synthesized to minimize and offset the AT bias for doubly cationic ligands bound in the minor groove of DNA. The compounds possess an N-formyl group in place of the guanidinium moiety normally present in netropsin. By systematic replacement of the N-methylpyrrole groups of the dipeptide with N-methylimidazole, a remarkably high degree of sequence specificity was obtained. One of the compounds having two N- methylimidazole residues was found to exhibit dramatically altered specificity when compared with netropsin and preferred to bind to the sequence. The structural elements underlying sequence recognition in terms of the model for the netropsin-DNA interaction are presented and discussed.
ASJC Scopus subject areas