A Caltech Library Service

NMR Characterization of the Aliphatic β/β Pairing for Recognition of A·T/T·A Base Pairs in the Minor Groove of DNA

Peláez Lamamie de Clairac, Rafael and Seel, Christian J. and Geierstanger, Bernhard H. and Mrksich, Milan and Baird, Eldon E. and Dervan, Peter B. and Wemmer, David E. (1999) NMR Characterization of the Aliphatic β/β Pairing for Recognition of A·T/T·A Base Pairs in the Minor Groove of DNA. Journal of the American Chemical Society, 121 (13). pp. 2956-2964. ISSN 0002-7863. doi:10.1021/ja983671u.

[img] PDF (Listings of chemical shifts for the ligand protons in the complexes, intermolecular contacts in the G2 complex at 25 and 45 °C, chemical shifts for the DNA protons of the G/G (at 25 and 45 °C), β/β, and Py/Py complexes, and intermolecular ligand−DNA ...) - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Because the curvature of four or five contiguous Im−Py rings does not perfectly match the canonical B-helix, β-alanine (β) residues have been inserted to reset the register. Complexes of three pyrrole−imidazole polyamides of sequence composition ImPyPy-X-PyPyPy-Dp, where X = Py, β, or glycine (G), bound to a 13 base 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 polyamide adopts an extended antiparallel dimeric conformation with the ligands fully overlapped around a central Py/Py, G/G, or β/β pair. Conformational exchange is seen near the linker for the G-linked complex, but not with the β or Py linkers. In addition to providing the first direct structural evidence for formation of the aliphatic β/β pairing in the minor groove, models support the idea that the β linker of ImPyPy-β-PyPyPy-Dp provides an optimal combination of size, flexibility, and alignment of the polyamide-paired aromatic subunits in extended, dimeric 2:1 complexes.

Item Type:Article
Related URLs:
URLURL TypeDescription Information
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1999 American Chemical Society. Received October 19, 1998. Revised Manuscript Received February 1, 1999. Publication Date (Web): March 19, 1999. We are grateful to the National Institutes of Health (Grant GM 43129 to D.E.W. and Grant GM 27681 to P.B.D.) and the National Foundation for Cancer Research for research support, to the Ralph M. Parson Foundation for a graduate fellowship to M.M., to the Howard Hughes Medical Institute for a predoctoral fellowship to E.E.B, and to the U.S. Department of Energy and the National Science Foundation for instrumentation grants. R.P.L.d.C. and C.J.S. gratefully acknowledge postdoctoral fellowships from the Fundación Ramón Areces and the Deutsche Forschungsgemeinschaft, respectively. R.P.L.d.C., B.H.G., and D.E.W. also thank T. D. Cole and P. A. Fagan for helpful discussions.
Funding AgencyGrant Number
National Foundation for Cancer ResearchUNSPECIFIED
Ralph M. Parsons FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Department of Energy (DOE)UNSPECIFIED
Fundación Ramón ArecesUNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Issue or Number:13
Record Number:CaltechAUTHORS:20160510-091950438
Persistent URL:
Official Citation:NMR Characterization of the Aliphatic β/β Pairing for Recognition of A·T/T·A Base Pairs in the Minor Groove of DNA Rafael Peláez Lamamie de Clairac, Christian J. Seel, Bernhard H. Geierstanger, Milan Mrksich, Eldon E. Baird, Peter B. Dervan, and David E. Wemmer Journal of the American Chemical Society 1999 121 (13), 2956-2964 DOI: 10.1021/ja983671u
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66853
Deposited By: Victoria Brennan
Deposited On:10 May 2016 19:10
Last Modified:11 Nov 2021 00:23

Repository Staff Only: item control page