Recognition of Nine Base Pairs in the Minor Groove of DNA by a Tripyrrole Peptide-Hoechst Conjugate
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- 作者：Alexander L. Satz and Thomas C. Bruice
- 刊名：Journal of the American Chemical Society
- 出版年：2001
- 出版时间：March 21, 2001
- 年：2001
- 卷：123
- 期：11
- 页码：2469 - 2477
- 全文大小：170K
- 年卷期：v.123,no.11(March 21, 2001)
- ISSN：1520-5126
文摘
A tripyrrole peptide-Hoechst conjugate (FPH-1) has been designed which recognizes nine dA/dTbase pair A/T rich dsDNA sequences at subnanomolar concentrations and complexes its targets at near diffusioncontrolled rates to form a fluorescent product. Spectrofluorometric titrations show the stoichiometry of thecomplex to be (FPH-1)2:dsDNA. Spectrofluorometric titrations were also employed to determine the productof the equilibrium constant for complexation (K1K2) of dsDNA by two FPH-1 molecules for 35 differentoligomeric duplexes. Single base pair mismatches in the FPH-1 binding site were found to cause significantdecreases in K1K2 of 18- to 2300-fold. Thermal denaturation experiments provided similar results. Argumentsare presented which favor the structure of the (FPH-1)2:dsDNA minor groove complex to involve the twoFPH-1 molecules in a slightly staggered, side-by-side, and antiparallel arrangement such that the bis-benzimidazole moiety of one FPH-1 molecule lies adjacent to the tripyrrole moiety of the second FPH-1molecule.