DNA binding of a short lexitropsin

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. and Waigh, R.D. (2004) DNA binding of a short lexitropsin. Bioorganic & Medicinal Chemistry Letters, 14 (5), 1353-1356. (doi:10.1016/j.bmcl.2003.11.068).

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.
Graphical Abstract
Footprinting, capillary electrophoresis, molecular modelling and NMR studies have been used to examine the binding of 5 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.

This record has no associated files available for download.

Contributors

Author: K.R. Fox

Download statistics