Facile synthesis of oligopeptide distamycin analogs devoid of hydrogen bond donors or acceptors at the N-terminus: sequence-specific duplex DNA binding as a function of peptide chain length

Abstract

The first examples of distamycin analogs, which lack hydrogen bond interactor groups at the N-terminus, have been synthesized. The bispyrrole peptide did not exhibit any detectable binding with double-stranded (ds) DNA. However, all other homologues did bind to ds-DNA strongly, with the binding affinities increasing as a function of the number of repeating pyrrole carboxamide units, implying that a hydrogen bond donor or acceptor atom per se at the N-terminus is not essential for their DNA binding. Studies with poly d(GC) showed that the N-terminal formamide is not a prerequisite for GC binding, contrary to earlier postulations.