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- Nielsen, P. E., et al.
(författare)
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DNA-BINDING AND PHOTOCLEAVAGE BY URANYL(VI) (UO2(2+)) SALTS
- 1992
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 114:13, s. 4967-4975
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of the uranyl(VI) ion (UO22+) with DNA and its light-induced cleavage of DNA has been studied using flow-linear dichroism and P-32-endlabeled oligonucleotides. It was found that binding of uranyl ion to DNA is a prerequisite for photocleavage; from run-off experiments the binding constant was estimated to be of the order of 10(10) M-1 at pH 4. The angular orientation of the [O=U=O]2+ chromophore is consistent with binding by bridging phosphate groups on opposite strands of the minor groove of DNA; at higher DNA concentration aggregation indicates intermolecular bridging as well. The uranyl-mediated photocleavage of DNA is not influenced by the presence of O2, is more efficient at low pH (
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| 2. |
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| 3. |
- 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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| 4. |
- Kim, Seog K., et al.
(författare)
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RIGHT-HANDED TRIPLEX FORMED BETWEEN PEPTIDE NUCLEIC-ACID PNA-T(8) AND POLY(DA) SHOWN BY LINEAR AND CIRCULAR-DICHROISM SPECTROSCOPY
- 1993
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 115:15, s. 6477-6481
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Tidskriftsartikel (refereegranskat)abstract
- The binding of an eightmer of peptide nucleic acid, H-T8-Lys-NH2 (=PNA-T8), to a polynucleotide, poly(dA), was studied by flow linear dichroism (LD) and circular dichroism (CD) spectroscopy. Whereas the single stranded DNA, due to its high flexibility, does not display any measurable LD signal when subjected to shear flow, the complex with PNA does. A titration shows that saturation occurs at a stoichiometry of two PNA thymine bases per DNA adenine base, indicating the formation of a triplex PNA2-DNA complex. The persistence length of the adduct remains small up to relatively high stoichiometries (above 1:1 T:A) indicating that no significant amounts of PNA:DNA duplex are formed. Instead triplex stretches seem to form surrounded by flexible parts of single stranded poly(dA). Upon approaching the stoichiometry 2:1 of T:A the LD increases dramatically demonstrating that the stiffness of the PNA-DNA triplex arises from base-base contacts preventing bending of the chain. It is also inferred that the main stiffness of duplex DNA very probably has a similar origin and is not primarily a result of the increased phosphate-phosphate repulsion. Circular dichroism spectra support the conclusion that a triplex is formed as the only PNA-DNA complex and that it is a right-handed helix. The wavelength dependence of the reduced linear dichroism shows that the inclination of the bases from perpendicularity relative to the helix axis is small. The base conformation of the poly(dA)[PNA-T8]2 triplex is very similar to that of the conventional poly(dA)[poly(dT)]2 triplex.
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