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Minimization of a Protein−DNA Dimerizer

Stafford, Ryan L. and Arndt, Hans-Dieter and Brezinski, Mary L. and Ansari, Aseem Z. and Dervan, Peter B. (2007) Minimization of a Protein−DNA Dimerizer. Journal of the American Chemical Society, 129 (9). pp. 2660-2668. ISSN 0002-7863. PMCID PMC3064071. doi:10.1021/ja067971k.

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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 ε-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 °C. These observations provide design principles for artificial transcription factors that may function in concert with the cellular regulatory circuitry.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Arndt, Hans-Dieter0000-0002-0792-1422
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2007 American Chemical Society. Received November 7, 2006. Published on Web 02/10/2007. This work was supported by the National Institute of Health (Research Grants to P.B.D. and A.Z.A). A DAAD postdoctoral fellowship (to H.D.A) is gratefully acknowledged. We thank Professor A. L. Aggarwal (Mount Sinai School of Medicine, New York) for a donation of the plasmid encoding the Exd DNA binding domain and Drs. P. Snow and G. Hathaway (Beckman Institute, California Institute of Technology) for technical assistance with protein expression, purification, and identification.
Funding AgencyGrant Number
Deutscher Akademischer Austauschdienst (DAAD)UNSPECIFIED
Issue or Number:9
PubMed Central ID:PMC3064071
Record Number:CaltechAUTHORS:20160509-110447840
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Official Citation:Minimization of a Protein−DNA Dimerizer Ryan L. Stafford, Hans-Dieter Arndt, Mary L. Brezinski, Aseem Z. Ansari, and Peter B. Dervan Journal of the American Chemical Society 2007 129 (9), 2660-2668 DOI: 10.1021/ja067971k
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66751
Deposited By: Victoria Brennan
Deposited On:17 May 2016 21:10
Last Modified:11 Nov 2021 00:02

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