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.