Minimization of a Protein-DNA Dimerizer
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- 作者：Ryan L. Stafford ; Hans-Dieter Arndt ; Mary L. Brezinski ; Aseem Z. Ansari ; and ; Peter B. Dervan
- 刊名：Journal of the American Chemical Society
- 出版年：2007
- 出版时间：March 7, 2007
- 年：2007
- 卷：129
- 期：9
- 页码：2660 - 2668
- 全文大小：759K
- 年卷期：v.129,no.9(March 7, 2007)
- ISSN：1520-5126
文摘
A protein-DNA dimerizer constructed from a DNA-binding polyamide and the peptide FYPWMKGfacilitates the binding of a natural transcription factor Exd to an adjacent DNA site. The Exd binding domaincan be reduced to a dipeptide WM attached to the polyamide through an 
lon.gif" BORDER=0 >-aminohexanoic acid linker withretention of protein-DNA dimerizer activity. Screening a library of analogues indicated that the tryptophanindole 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
ll.gif">Exdll.gif">DNA ternarycomplex at 37 
C. These observations provide design principles for artificial transcription factors that mayfunction in concert with the cellular regulatory circuitry.
lon.gif" BORDER=0 >-aminohexanoic acid linker withretention of protein-DNA dimerizer activity. Screening a library of analogues indicated that the tryptophanindole 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 dimerizerll.gif">Exdll.gif">DNA ternarycomplex at 37 C. These observations provide design principles for artificial transcription factors that mayfunction in concert with the cellular regulatory circuitry.