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Science 2 October 1998:
Vol. 282. no. 5386, pp. 111 - 115
DOI: 10.1126/science.282.5386.111
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Reports

A Structural Basis for Recognition of A·T and T·A Base Pairs in the Minor Groove of B-DNA

Clara L. Kielkopf, Sarah White, Jason W. Szewczyk, James M. Turner, Eldon E. Baird, Peter B. Dervan, * Douglas C. Rees *

Polyamide dimers containing three types of aromatic rings--pyrrole, imidazole, and hydroxypyrrole--afford a small-molecule recognition code that discriminates among all four Watson-Crick base pairs in the minor groove. The crystal structure of a specific polyamide dimer-DNA complex establishes the structural basis for distinguishing T·A from A·T base pairs. Specificity for the T·A base pair is achieved by means of distinct hydrogen bonds between pairs of substituted pyrroles on the ligand and the O2 of thymine and N3 of adenine. In addition, shape-selective recognition of an asymmetric cleft between the thymine-O2 and the adenine-C2 was observed. Although hitherto similarities among the base pairs in the minor groove have been emphasized, the structure illustrates differences that allow specific minor groove recognition.

C. L. Kielkopf, Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. S. White, J. W. Szewczyk, J. M. Turner, E. E. Baird, P. B. Dervan, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. D. C. Rees, Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
*   To whom correspondence should be addressed. E-mail: dervan{at}its.caltech.edu (P.B.D.); dcrees{at}its.caltech.edu (D.C.R.)

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