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Published August 8, 1996 | public
Journal Article

Recognition of DNA by designed ligands at subnanomolar concentrations

Abstract

SMALL molecules that specifically bind with high affinity to any predetermined DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to control rationally the sequence specificity of minor-groove-binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids. Two eight-ring pyrrole–imidazole polyamides differing in sequence by a single amino acid bind specifically to respective six-base-pair target sites which differ in sequence by a single base pair. Binding is observed at subnanomolar concentrations of ligand. The replacement of a single nitrogen atom with a C-H regulates affinity and specificity by two orders of magnitude. The broad range of sequences that can be specifically targeted with pyrrole–imidazole polyamides, coupled with an efficient solid-phase synthesis methodology, identify a powerful class of small molecules for sequence-specific recognition of double-helical DNA.

Additional Information

© 1996 Nature Publishing Group. Received 22 March; accepted 25 June 1996. We are grateful to the NIH for research support, to the NSF for a predoctoral fellowship to J.W.T., and to the HHMI for a predoctoral fellowship to E.E.B.

Additional details

Created:
August 19, 2023
Modified:
October 23, 2023