NMR Characterization of the Aliphatic /
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- 作者：Rafael Pelá ; ez Lamamie de Clairac ; Christian J. Seel ; Bernhard H. Geierstanger ; Milan Mrksich ; Eldon E. Baird ; Peter B. Dervan ; and David E. Wemmer
- 刊名：Journal of the American Chemical Society
- 出版年：1999
- 出版时间：April 7, 1999
- 年：1999
- 卷：121
- 期：13
- 页码：2956 - 2964
- 全文大小：352K
- 年卷期：v.121,no.13(April 7, 1999)
- ISSN：1520-5126
文摘
Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can becombined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor grooveof DNA. Because the curvature of four or five contiguous Im-Py rings does not perfectly match the canonicalB-helix, 
-alanine () residues have been inserted to reset the register. Complexes of three pyrrole-imidazolepolyamides of sequence composition ImPyPy-X-PyPyPy-Dp, where X = Py, , or glycine (G), bound to a 13base pair DNA duplex containing a 9 base pair 5'-TGTATATCA-3' match site were characterized by NMR.NMR titrations and NOESY data combined with restrained molecular modeling show that each polyamideadopts an extended antiparallel dimeric conformation with the ligands fully overlapped around a central Py/Py, G/G, or / pair. Conformational exchange is seen near the linker for the G-linked complex, but not withthe or Py linkers. In addition to providing the first direct structural evidence for formation of the aliphatic/ pairing in the minor groove, models support the idea that the linker of ImPyPy--PyPyPy-Dp providesan optimal combination of size, flexibility, and alignment of the polyamide-paired aromatic subunits in extended,dimeric 2:1 complexes.
-alanine () residues have been inserted to reset the register. Complexes of three pyrrole-imidazolepolyamides of sequence composition ImPyPy-X-PyPyPy-Dp, where X = Py, , or glycine (G), bound to a 13base pair DNA duplex containing a 9 base pair 5'-TGTATATCA-3' match site were characterized by NMR.NMR titrations and NOESY data combined with restrained molecular modeling show that each polyamideadopts an extended antiparallel dimeric conformation with the ligands fully overlapped around a central Py/Py, G/G, or / pair. Conformational exchange is seen near the linker for the G-linked complex, but not withthe or Py linkers. In addition to providing the first direct structural evidence for formation of the aliphatic/ pairing in the minor groove, models support the idea that the linker of ImPyPy--PyPyPy-Dp providesan optimal combination of size, flexibility, and alignment of the polyamide-paired aromatic subunits in extended,dimeric 2:1 complexes.