NMR Characterization of Hairpin Polyamide Complexes with the Minor Groove of DNA
详细信息 查看全文
- 作者：Rafael Pelá ; ez Lamamie de Clairac ; Bernhard H. Geierstanger ; Milan Mrksich ; Peter B. Dervan ; and David E. Wemmer
- 刊名：Journal of the American Chemical Society
- 出版年：1997
- 出版时间：August 27, 1997
- 年：1997
- 卷：119
- 期：34
- 页码：7909 - 7916
- 全文大小：290K
- 年卷期：v.119,no.34(August 27, 1997)
- ISSN：1520-5126
文摘
Polyamides containing N-methylimidazole (Im) andN-methylpyrrole (Py) amino acids can becombinedin antiparallel side-by-side dimeric complexes for sequence-specificrecognition in the minor groove of DNA.Covalently linking polyamide subunits has led to designed ligandswith both increased affinity and specificity. Simplealiphatic amino acid linkers serve as internal guide residues for turnvs extended binding in a head-to-tail-linkedpolyamide motif. Polyamides of sequence compositionImPyPy-X-PyPyPy containing linkers of incremental length(X = 3-aminopropionic acid (
), 4-aminobutyric acid (
), or5-aminovaleric acid (
)) in complex with an undecamerDNA duplex containing a 5'-(A,T)G(A,T)3-3' target sitewere structurally characterized using NMR spectroscopy.Previous quantitative DNase I footprinting studies identified as the highest affinity of these "turn" linkers.NMRtitrations and 2D NOESY data combined with restrained molecularmodeling reveal that polyamides with , , and linkers all may adopt a hairpin structure. Modeling supportsthe idea that the linkers in the and complexesadopt an energetically less favorable turn geometry than the linkerand confirms that the three-carbon linker issufficient and optimal for the hairpin conformation.
), 4-aminobutyric acid (), or5-aminovaleric acid ()) in complex with an undecamerDNA duplex containing a 5'-(A,T)G(A,T)3-3' target sitewere structurally characterized using NMR spectroscopy.Previous quantitative DNase I footprinting studies identified as the highest affinity of these "turn" linkers.NMRtitrations and 2D NOESY data combined with restrained molecularmodeling reveal that polyamides with , , and linkers all may adopt a hairpin structure. Modeling supportsthe idea that the linkers in the and complexesadopt an energetically less favorable turn geometry than the linkerand confirms that the three-carbon linker issufficient and optimal for the hairpin conformation.