High Affinity, Sequence Specific DNA Binding by Synthetic Tripyrrole–Peptide Conjugates

Linking the basic region of a bZIP transcription factor to a distamycin‐like tripyrrole peptide by means of a nitrogen‐containing tether produces a hybrid capable of high‐affinity recognition of specific, designated DNA sequences. The importance of the nitrogen in the tether is shown by the considerable reduction in affinity (more than 10‐fold) caused by its replacement with an ether linkage. Attachment of an aminopropyl chain on the pyrrole adjacent to the pyrrole bearing the nitrogen‐containing tether increases affinity approximately one order of magnitude. These results confirm that a suitable location of protonated amine groups on designed DNA‐binding peptides provides for higher affinities, most probably because of the generation of salt bridged contacts with the phosphodiester backbone.