Toward rules for 1:1 polyamide:DNA recognition

Creators: Urbach, Adam R.; Dervan, Peter B.

Abstract

Polyamides composed of four amino acids, imidazole (Im), pyrrole (Py), hydroxypyrrole (Hp), and beta -alanine (beta) are synthetic ligands that form highly stable complexes in the minor groove of DNA. Although specific pairing rules within the 2:1 motif can be used to distinguish the four Watson Crick base pairs, a comparable recognition code for 1:1 polyamide:DNA complexes had not been described. To set a quantitative baseline for the field, the sequence specificities of Im, Py, Hp, and beta for the four Watson Crick base pairs were determined for two polyamides, Im-beta -ImPy-beta -Im-beta -ImPy-beta -DP (1, for Im, Py, and beta) and Im-beta -ImHp-beta -Im-beta -ImPy-beta -Dp (2, for Hp), in a 1:1 complex within the DNA sequence context 5'-AAA-GAGAAGAG-3'. Im residues do not distinguish C,C from A,T but bind all four base pairs with high affinity. Py and beta residues exhibit greater than or equal to 10-fold preference for A,T over G,C base pairs. The Hp residue displays a unique preference for a single A.T base pair with an energetic penalty.

Additional Information

Copyright © 2001 by the National Academy of Sciences. Contributed by Peter B. Dervan, February 12, 2001. We thank the National Institutes of Health (Grant 27687) for research support and a training fellowship (to A.R.U.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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