title: The reach of linear protein-DNA dimerizers.
abstract: A protein-DNA dimerizer constructed from a DNA-binding pyrrole-imidazole polyamide and the peptide FYPWMK facilitates binding of the natural transcription factor Exd to an adjacent DNA site. Previous dimerizers have been constructed with the peptide attached to an internal pyrrole monomer in an overall branched oligomer. Linear oligomers constructed by attaching the peptide to the polyamide C-terminus expand the range of protein-DNA dimerization to six additional DNA sites. Replacing the FYPWMK hexapeptide with a WM dipeptide, which was previously functional in branched compounds, does not lead to a functional linear dimerizer. Instead, inserting an additional lysine generates a minimal, linear WMK tripeptide conjugate that maintains the activity of the larger FYPWMK dimerizers in a single DNA-binding site orientation. These studies provide insight into the importance of linker length and composition, binding site spacing and orientation, and the protein-binding domain content that are important for the optimization of protein-DNA dimerizers suitable for biological experiments.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Stafford
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D008968:Molecular Conformation; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D009757:Nylons; D010455:Peptides; D011506:Proteins; D004247:DNA