DNA binding of a short lexitropsin

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 5; pp. 1353 - 1356
• Main Authors: ANTHONY, Nahoum G, FOX, Keith R, JOHNSTON, Blair F, KHALAF, Abedawn I, MACKAY, Simon P, MCGROARTY, Lain S, PARKINSON, John A, SKELLERN, Graham G, SUCKLING, Colin J, WAIGH, Roger D
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 08.03.2004
• Subjects: Binding Sites; Biological and medical sciences; DNA - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Medical sciences; Miscellaneous; Netropsin - analogs & derivatives; Netropsin - chemistry; Netropsin - metabolism; Pharmacology. Drug treatments; Protein Binding; Sequence specificity; Biological fixation; Nylon; Oligopeptides; Peptides; Structure activity relation; Minor groove; DNA; Pyrrole derivative polymer; Molecular interaction; Oligomer
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.11.068

Footprinting, capillary electrophoresis, molecular modelling and NMR studies have been used to examine the binding of a short polyamide to DNA. This molecule, which contains an isopropyl-substituted thiazole in place of one of the N-methylpyrroles, is selective for the sequence 5'-ACTAGT-3' to which it binds with high affinity. Two molecules bind side-by-side in the minor groove, but their binding is staggered so that the molecule reads six base pairs, unlike the related natural products, which tend to bind to four-base-pair sequences. The result suggests that high affinity and selectivity may be gained without resort to very large molecules, which may be difficult to deliver to the site of action.