Sequence-Dependent Drug Binding to the Minor Groove of DNA: Crystal Structure of the DNA Dodecamer d(CGCAAATTTGCG)2 Complexed with Propamidine

Nunn, Christine M. and Neidle, Stephen (1995) Sequence-Dependent Drug Binding to the Minor Groove of DNA: Crystal Structure of the DNA Dodecamer d(CGCAAATTTGCG)2 Complexed with Propamidine. Journal of Medicinal Chemistry, 38 (13). pp. 2317-2325. ISSN 0022-2623

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Official URL: http://dx.doi.org/10.1021/jm00013a008

Abstract

The DNA-binding ligand propamidine, an analogue of the drug pentamidine which is used in the treatment of acquired immune deficiency syndrome (AIDS)-associated Pneumocystis carinii, has been cocrystallized with the DNA sequence d(CGCAAATTTGCG)2, and the crystal structure of the complex has been determined using data from 8 to 2.2 A resolution. The R factor converged to 15.5% with the inclusion of 73 water molecules. The structure shows binding of the propamidine molecule within the AT tract of the DNA minor groove with a shift from the center of the duplex toward the 3’ end of ca. 2 A. The long AT tract of six base pairs in length allows the propamidine many potential binding sites in the DNA groove, and its binding is seen to occur where there is least perturbation to the DNA from that seen in the native structure. The interactions with bases are distinct from those previously observed for the sequence d(CGCGAATTCGCG)2.

Item Type: Article
Uncontrolled Keywords: DNA-binding ligand propamidine, DNA sequence d(CGCAAATTTGCG)2, deoxyribonucleic acid
Subjects: 500 Natural Sciences and Mathemetics > 540 Chemistry & allied sciences
600 Technology > 610 Medicine & health
Department: School of Human Sciences
Depositing User: Christine Nunn
Date Deposited: 03 Aug 2015 09:41
Last Modified: 21 Aug 2015 08:23
URI: http://repository.londonmet.ac.uk/id/eprint/732

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