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.
- capillary electrophoresis
- short polyamide to DNA
- isopropyl-substituted thiazole
- side-by-side in the minor groove
- high affinity
- applied chemistry
Anthony, N. G., Fox, K. R., Johnston, B. F., Khalaf, A. I., Mackay, S. P., McGroarty, I. S., Parkinson, J. A., Skellern, G. G., Suckling, C. J., & Waigh, R. D. (2004). DNA binding of a short lexitropsin. Bioorganic and Medicinal Chemistry Letters, 14(5), 1353-1356. https://doi.org/10.1016/j.bmcl.2003.11.068