Design of a Covalent Peptide Heterodimer for Sequence-Specific Recognition in the Minor Groove of Double-Helical DNA

While 1:1 peptide-DNA models aided in the design of for recognition of long tracts of contiguous A,T pairs of DNA, early efforts to design peptides for recognition mixed A,T and G,C sequences met with limited success. The peptides 2-PyN and2-ImN, targeted to the 5'-TGTTA- 3' site as 1:1 complexes, were found to bind the unanticipated 5'-TGTCA-3' as anti parallel side-by-side dimers in the groove. These and other recent 2:1 peptide-DNA offer a revised model for the design of ligands for -specific recognition in the minor groove of DNA. In to sequence-dependent minor groove width being a of specificity, the 2:1 model allows specific contacts each strand on the floor of the minor groove. Based on this understanding, we report here a successful second generation , a covalent peptide heterodimer, which specifically binds designated sequence 5'-TGTTA-3'.