Inhibition of major-groove-binding proteins by pyrrole-imidazole polyamides with an Arg-Pro-Arg positive patch
Abstract
Gene-specific targeting of any protein-DNA complex by small molecules is a challenging goal at the interface of chemistry and biology. Polyamides containing N-methylimidazole and N-methylpyrrole amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to many naturally occurring DNA-binding proteins. It has been shown that an eight-ring hairpin polyamide targeted to a specific minor-groove contact within a transcription factor binding site can inhibit protein-DNA binding and gene transcription. Polyamides and certain major-groove-binding proteins have been found to co-occupy the DNA helix, however. To expand the number of genes that can be targeted by pyrrole/imidazole polyamides, we set out to develop a class of polyamides that can selectively inhibit major-groove-binding proteins.
Additional Information
© 1998 Elsevier Ltd. Received 28 November 1997, Revised 30 December 1997, and 15 January 1998, Accepted 16 January 1998, Available online 8 December 2003. We are grateful to the National Institutes of Health General Medical Sciences for research support, to the National Science Foundation for a predoctoral fellowship to R.E.B., and to the Howard Hughes Medical institute for a predoctoral fellowship to E.E.B.Additional details
- Eprint ID
- 66868
- DOI
- 10.1016/S1074-5521(98)90057-6
- Resolver ID
- CaltechAUTHORS:20160510-094623856
- NSF Predoctoral Fellowship
- NIH
- Howard Hughes Medical Institute (HHMI)
- Created
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2016-05-18Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field