Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jul 9;93(14):6981–6985. doi: 10.1073/pnas.93.14.6981

Binding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif.

J J Kelly 1, E E Baird 1, P B Dervan 1
PMCID: PMC38920  PMID: 8692930

Abstract

Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity.

Full text

PDF
6981

Images in this article

6983Fig. 4
on p.6983

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bailly C., Pommery N., Houssin R., Henichart J. P. Design, synthesis, DNA binding, and biological activity of a series of DNA minor-groove-binding intercalating drugs. J Pharm Sci. 1989 Nov;78(11):910–917. doi: 10.1002/jps.2600781106. [DOI] [PubMed] [Google Scholar]
  2. Brenowitz M., Senear D. F., Shea M. A., Ackers G. K. "Footprint" titrations yield valid thermodynamic isotherms. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8462–8466. doi: 10.1073/pnas.83.22.8462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen X., Ramakrishnan B., Rao S. T., Sundaralingam M. Binding of two distamycin A molecules in the minor groove of an alternating B-DNA duplex. Nat Struct Biol. 1994 Mar;1(3):169–175. doi: 10.1038/nsb0394-169. [DOI] [PubMed] [Google Scholar]
  4. Geierstanger B. H., Jacobsen J. P., Mrksich M., Dervan P. B., Wemmer D. E. Structural and dynamic characterization of the heterodimeric and homodimeric complexes of distamycin and 1-methylimidazole-2-carboxamide-netropsin bound to the minor groove of DNA. Biochemistry. 1994 Mar 15;33(10):3055–3062. doi: 10.1021/bi00176a039. [DOI] [PubMed] [Google Scholar]
  5. Geierstanger B. H., Mrksich M., Dervan P. B., Wemmer D. E. Design of a G.C-specific DNA minor groove-binding peptide. Science. 1994 Oct 28;266(5185):646–650. doi: 10.1126/science.7939719. [DOI] [PubMed] [Google Scholar]
  6. Geierstanger B. H., Mrksich M., Dervan P. B., Wemmer D. E. Extending the recognition site of designed minor groove binding molecules. Nat Struct Biol. 1996 Apr;3(4):321–324. doi: 10.1038/nsb0496-321. [DOI] [PubMed] [Google Scholar]
  7. Mrksich M., Wade W. S., Dwyer T. J., Geierstanger B. H., Wemmer D. E., Dervan P. B. Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7586–7590. doi: 10.1073/pnas.89.16.7586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Pelton J. G., Wemmer D. E. Structural characterization of a 2:1 distamycin A.d(CGCAAATTGGC) complex by two-dimensional NMR. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5723–5727. doi: 10.1073/pnas.86.15.5723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Schultz P. G., Dervan P. B. Sequence-specific double-strand cleavage of DNA by penta-N-methylpyrrolecarboxamide-EDTA X Fe(II). Proc Natl Acad Sci U S A. 1983 Nov;80(22):6834–6837. doi: 10.1073/pnas.80.22.6834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Van Dyke M. M., Dervan P. B. Echinomycin binding sites on DNA. Science. 1984 Sep 14;225(4667):1122–1127. doi: 10.1126/science.6089341. [DOI] [PubMed] [Google Scholar]
  11. Wade W. S., Mrksich M., Dervan P. B. Binding affinities of synthetic peptides, pyridine-2-carboxamidonetropsin and 1-methylimidazole-2-carboxamidonetropsin, that form 2:1 complexes in the minor groove of double-helical DNA. Biochemistry. 1993 Oct 26;32(42):11385–11389. doi: 10.1021/bi00093a015. [DOI] [PubMed] [Google Scholar]
  12. Youngquist R. S., Dervan P. B. Sequence-specific recognition of B-DNA by oligo(N-methylpyrrolecarboxamide)s. Proc Natl Acad Sci U S A. 1985 May;82(9):2565–2569. doi: 10.1073/pnas.82.9.2565. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES