| 1. |
- Egholm, M., et al.
(författare)
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PNA HYBRIDIZES TO COMPLEMENTARY OLIGONUCLEOTIDES OBEYING THE WATSON-CRICK HYDROGEN-BONDING RULES
- 1993
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 365:6446, s. 566-568
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Tidskriftsartikel (refereegranskat)abstract
- DNA ANALOGUES are currently being intensely investigated owing to their potential as gene-targeted drugs1-3. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties3,4. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached5-9. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes5-7, and bind to double-stranded DNA by strand displacement5,8. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.
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| 2. |
- Wittung, Pernilla, 1968, et al.
(författare)
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INTERACTIONS OF DNA-BINDING LIGANDS WITH PNA DNA HYBRIDS
- 1994
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 22:24, s. 5371-5377
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Tidskriftsartikel (refereegranskat)abstract
- The interactions of two representative mixed-sequence (one with an AT-stretch) PNA - DNA duplexes (10 or 15 base-pairs) and a PNA(2)/DNA tripler with the DNA binding reagents distamycin A, 4',6-diamidino-2-phenylindole (DAPI), ethidium bromide, 8-methoxy-psoralen and the Delta and Lambda enantiomers of Ru(phen)(2)-dppz(2+) have been investigated using optical spectroscopic methods. The behaviour of these reagents versus two RNA-PNA duplexes has also been investigated. With triple helical poly(dA)/(H-T-10-Lys-NH2)(2) no significant intercalative binding was detected for any of the DNA intercalators, whereas DAPI, a DNA minor groove binder, was found to exhibit a circular dichroism 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 distamycin 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 RNA-DNA duplex consisting of a ten base-pair mixed purine-pyrimidine 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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