Molecular recognition between oligopeptides and nucleic acids. Monocationic imidazole lexitropsins that display enhanced GC sequence dependent DNA binding

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Abstract
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 3''-GGCA-5''5''-CCGT-3''. The structural elements underlying sequence recognition in terms of the model for the netropsin-DNA interaction are presented and discussed.