Abstract
Dien-microgonotropen-c (5c), tren-microgonotropen-b (6b), and distamycin (Dm) bind the A.T-rich region of d(CGCAAATTTGCG)2 (oligo-12) and form 1:1 (5c and 6b) and 2:1 and 4:1 (Dm) complexes. At 1.75 mol ratio of Dm/oligo-12 the 4:1 complex starts to form and coexists with the 2:1 complex and the free double-stranded DNA. No 1:1 and 3:1 complexes were seen, implying a preferential dimeric binding mode of Dm to oligo-12. At 4:1 mol ratio of Dm/oligo-12 there is extensive exchange of the A.T imino protons with the solvent at the binding site. This is presumably due to the opening of the minor groove. Molecular modeling shows that four Dm molecules can fit in a tandem antiparallel way into the minor groove of oligo-12 by widening it to 16-17 A. On going from oligo-12 to the pseudosymmetrical hexadecamer oligo-16 [d(GGCGCAAATTTGGCGG).d(CCGCCAAATTTGCGCC)] the stoichiometry of binding of 5c changes from 1:1 to 2:1. Since oligo-12 and oligo-16 have the same A.T binding site this change in stoichiometry is due to the increase in the G.C terminal pairing. Hoechst 33258 displaces the two 5c molecules bound in the minor groove of oligo-16 at the A.T region. Marked exchange of A.T imino protons was seen in the case of (oligo-16).(Ht)2.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chen S. M., Leupin W., Rance M., Chazin W. J. Two-dimensional NMR studies of d(GGTTAATGCGGT).d(ACCGCATTAACC) complexed with the minor groove binding drug SN-6999. Biochemistry. 1992 May 12;31(18):4406–4413. doi: 10.1021/bi00133a004. [DOI] [PubMed] [Google Scholar]
- Coll M., Frederick C. A., Wang A. H., Rich A. A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8385–8389. doi: 10.1073/pnas.84.23.8385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fede A., Labhardt A., Bannwarth W., Leupin W. Dynamics and binding mode of Hoechst 33258 to d(GTGGAATTCCAC)2 in the 1:1 solution complex as determined by two-dimensional 1H NMR. Biochemistry. 1991 Dec 3;30(48):11377–11388. doi: 10.1021/bi00112a004. [DOI] [PubMed] [Google Scholar]
- Guéron M., Kochoyan M., Leroy J. L. A single mode of DNA base-pair opening drives imino proton exchange. Nature. 1987 Jul 2;328(6125):89–92. doi: 10.1038/328089a0. [DOI] [PubMed] [Google Scholar]
- Loontiens F. G., Regenfuss P., Zechel A., Dumortier L., Clegg R. M. Binding characteristics of Hoechst 33258 with calf thymus DNA, poly[d(A-T)], and d(CCGGAATTCCGG): multiple stoichiometries and determination of tight binding with a wide spectrum of site affinities. Biochemistry. 1990 Sep 25;29(38):9029–9039. doi: 10.1021/bi00490a021. [DOI] [PubMed] [Google Scholar]
- 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]
- Pelton J. G., Wemmer D. E. Structural modeling of the distamycin A-d(CGCGAATTCGCG)2 complex using 2D NMR and molecular mechanics. Biochemistry. 1988 Oct 18;27(21):8088–8096. doi: 10.1021/bi00421a018. [DOI] [PubMed] [Google Scholar]