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Published April 20, 1994 | metadata_only
Journal Article

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

Additional Information

© 1994 American Chemical Society. Received January 12, 1994. We are grateful to the National Institutes of Health (GM-27681) for research support and the Ralph M. Parsons Foundation for a Graduate Fellowship to M.M.

Additional details

August 20, 2023
August 20, 2023