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DNA binding of a short lexitropsin

Anthony, N.G. and Fox, K.R. and Johnston, B.F. and Khalaf, A.I. and Mackay, S.P. and McGroarty, I.S. and Parkinson, J.A. and Skellern, G.G. and Suckling, C.J. and Waigh, R.D. (2004) DNA binding of a short lexitropsin. Bioorganic and Medicinal Chemistry Letters, 14 (5). pp. 1353-1356. ISSN 0960-894X

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Abstract

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.