Research article summary (published 25 Oct 2004):

Thiophene-based diamidine forms a "super" at binding minor groove agent.

Full Abstract

The DNA minor groove is the interaction site for many enzymes and transcription control proteins and as a result, development of compounds that target the minor groove is an active research area. In an effort to develop biologically active minor groove agents, we are preparing and exploring the DNA interactions of a systematic set of diamidine derivatives with a powerful array of methods including DNase I footprinting, biosensor-SPR methods, and X-ray crystallography. Surprisingly, conversion of the parent phenyl-furan-phenyl diamidine to a phenyl-thiophene-benzimidazole derivative yields a compound with over 10-fold-increased affinity for the minor groove at AT sequences. Single conversion of the furan to a thiophene or a phenyl to benzimidazole does not cause a similar increase in affinity. X-ray results indicate a small bond angle difference between the C-S-C angle of thiophene and the C-O-C angle of furan that, when amplified out to the terminal amidines of the benzimidazole compounds, yields a very significant difference in the positions of the amidines and their DNA interaction strength. Copyright 2004 American Chemical Society

Author information

Author/s: Mallena, Sirish (S); Lee, Michael P H (MP); Bailly, Christian (C); Neidle, Stephen (S); Kumar, Arvind (A); Boykin, David W (DW); Wilson, W David (WD);

Affiliation: Department of Chemistry, Georgia State University, P.O. Box 4098, Atlanta, Georgia 30302-4098, USA.

Grants: GM61587 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: Journal of the American Chemical Society (J Am Chem Soc), published in United States. (Language: eng)

Reference: 2004-Oct; vol 126 (issue 42) : pp 13659-69

Dates: Created 2004/10/20; Completed 2004/11/23; Revised 2008/11/21;

PMID: 15493923, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adenine - chemistry; metabolism Animals Base Pairing Benzamidines - chemistry; metabolism; pharmacology Biosensing Techniques Calorimetry Cattle Chemistry, Physical Circular Dichroism Crystallography, X-Ray DNA - chemistry; metabolism

DNA Footprinting Deoxyribonuclease I - metabolism Models, Molecular Nucleic Acid Conformation Pentamidine - analogs & derivatives; chemistry; metabolism; pharmacology Physicochemical Phenomena Surface Plasmon Resonance Thermodynamics Thiophenes - chemistry; metabolism; pharmacology Thymine - chemistry; metabolism Titrimetry

Associated Chemicals: Benzamidines (0) ; Thiophenes (0) ; Pentamidine (100-33-4) ; Thymine (65-71-4) ; Adenine (73-24-5) ; furamidine (73819-26-8) ; DNA (9007-49-2) ; Deoxyribonuclease I (EC 3.1.21.1)

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