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Toward rules for 1:1 polyamide:DNA recognition

Urbach, Adam R. and Dervan, Peter B. (2001) Toward rules for 1:1 polyamide:DNA recognition. Proceedings of the National Academy of Sciences of the United States of America, 98 (8). pp. 4343-4348. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:URBpnas01

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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.


Item Type:Article
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.
Subject Keywords:SEQUENCE-SPECIFIC RECOGNITION; DOUBLE-HELICAL DNA; MINOR-GROOVE; BASE-PAIRS; IMIDAZOLE POLYAMIDES; B-DNA; MOTIF; PYRROLE; OLIGOPEPTIDES; DISTAMYCIN
Record Number:CaltechAUTHORS:URBpnas01
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:URBpnas01
Alternative URL:http://dx.doi.org/10.1073/pnas.081070798
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1587
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Feb 2006
Last Modified:26 Dec 2012 08:45

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