Nucleic Acids Research, 1994, Vol. 22, No. 24 5371-5377
© 1994
Articles |
Interactions of DNA binding ligands with PNA-DNA hybrids
Department of Physical Chemistry, Chalmers University of Technology S-41296 Gothenburg Sweden 1Department of Chemistry, College of Science, Yeungnam University Kyoungsan City, Kyoung-buk 712-749, Republic of Korea 2Department of Organic Chemistry, The H.C.0Ørsted Institute Universitetsparken 5, 2100 0Ø Copenhagen 3Center for Biomolecular Recognition, The Panum Institute, Department of Biochemistry B Blegdamsvej 3c, 2200 N Copenhagen, Denmark
*To whom correspondence should be addressed
Received August 5, 1994. Accepted November 1, 1994.
The Interactions of two representative mixed-sequence (one with an AT-stretch) PNA - DNA duplexes (10 or 15 base-pairs) and a PNA2/DNA triplex with the DNA binding reagents distamycln A, 4',6-diamidlno-2-phenylindole (DAPI), ethldium bromide, 8-methoxy-psoralen and the 
and enantiomers of Ru(phen)2-dppz2– have been Investigated using optical spectro-scopic methods. The behaviour of these reagents versus two PNA- PNA duplexes has also been Investigated. With triple helical poly(dA)/(H-T10-Lys-NH2)2 no significant intercalate binding was detected for any of the DNA Intercalators, whereas DAPI, a DNA minor groove binder, was found to exhibit a circular dlchroism with a positive sign and amplitude consistent with minor groove binding. Similarly, a PNA-DNA duplex containing a central AATA motif, a typical minor groove binding site for the DNA minor groove binders dlsta-mycin A and DAPI, showed binding for both of these drugs, though with strongly reduced affinity. No important interactions were found for any of the ligands with a PNA - DNA duplex consisting of a ten base-pair mixed purine-pyrlmldlne sequence with only two AT base-pairs in the centre. Nor did any of the ligands show any detectable binding to the PNA-PNA duplexes (one containing an AATT motif). Various PNA derivatives with extentions of the backbone, believed to increase the flexibility of the duplex to opening of an intercalation slot, were tested for intercalation of ethidium bromide or 8-methoxypsoralen into the mixed sequence PNA-DNA duplex, however, without any observation of improved binding. The importance of the Ionic contribution of the deoxyribose phosphate backbone, versus interactions with the nucleobases, for drug binding to DNA is discussed in the light of these findings.
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