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Minimization of a protein-DNA dimerizer.

ABSTRACT: A protein-DNA dimerizer constructed from a DNA-binding polyamide and the peptide FYPWMKG facilitates the binding of a natural transcription factor Exd to an adjacent DNA site. The Exd binding domain can be reduced to a dipeptide WM attached to the polyamide through an epsilon-aminohexanoic acid linker with retention of protein-DNA dimerizer activity. Screening a library of analogues indicated that the tryptophan indole moiety is more important than methionine's side chain or the N-terminal acetamide. Remarkably, switching the stereochemistry of the tryptophan residue (l to d) stabilizes the dimerizer*Exd*DNA ternary complex at 37 degrees C. These observations provide design principles for artificial transcription factors that may function in concert with the cellular regulatory circuitry.

SUBMITTER: Stafford RL

PROVIDER: S-EPMC3064071 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Minimization of a protein-DNA dimerizer.

Stafford Ryan L RL Arndt Hans-Dieter HD Brezinski Mary L ML Ansari Aseem Z AZ Dervan Peter B PB

Journal of the American Chemical Society 20070210 9

A protein-DNA dimerizer constructed from a DNA-binding polyamide and the peptide FYPWMKG facilitates the binding of a natural transcription factor Exd to an adjacent DNA site. The Exd binding domain can be reduced to a dipeptide WM attached to the polyamide through an epsilon-aminohexanoic acid linker with retention of protein-DNA dimerizer activity. Screening a library of analogues indicated that the tryptophan indole moiety is more important than methionine's side chain or the N-terminal aceta ...[more]

PMID: 17290996

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