| 1. |
- Dahl-Jensen, D., et al.
(författare)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 2. |
- 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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| 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. |
- Haaima, G., et al.
(författare)
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Peptide nucleic acids (PNA) derived from N-(N-methylaminoethyl)glycine. Synthesis, hybridization and structural properties
- 1999
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Ingår i: New Journal of Chemistry. - 1369-9261 .- 1144-0546. ; 23:8, s. 833-840
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Tidskriftsartikel (refereegranskat)abstract
- Backbone N-methylated peptide nucleic acids (PNAs) containing the four nucleobases adenine, cytosine, guanine and thymine were synthesized via solid phase peptide oligomerization. The oligomers bind to their complementary target with a thermal stability that is 1.5-4.5 degrees C lower per "N-methyl nucleobase unit" [dependent on the number and position(s) of the N-methyl] than that of unmodified PNA. However, even fully N-methyl modified PNAs bind as efficiently to DNA or RNA targets as DNA itself. Furthermore, the hybridization efficiency per N-methyl unit in a PNA decreased with increasing N-methyl content, and the effect was more pronounced when the N-methyl backbone units are present in the Hoogsteen versus the Watson-Crick strand in (PNA)(2)-DNA triplexes. Interestingly, CD spectral analyses indicate that 30% (3 out of ten) substitution with N-methyl nucleobases did not alter the structure of PNA-DNA (or RNA) duplexes or (PNA)(2)-DNA triplexes, and likewise CD spectroscopy and X-ray crystallography showed no major structural differences between N-methylated (30%) and unmodified PNA-PNA duplexes. However, PNA-DNA duplexes as well as triplexes adopted a different conformation when formed with all-Ai-methyl PNAs.
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| 5. |
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| 6. |
- Hyrup, B., et al.
(författare)
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STRUCTURE-ACTIVITY STUDIES OF THE BINDING OF MODIFIED PEPTIDE NUCLEIC-ACIDS (PNAS) TO DNA
- 1994
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 116:18, s. 7964-7970
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Tidskriftsartikel (refereegranskat)abstract
- Peptide nucleic acid (PNA) oligomers where one of the repeating backbone units is extended with a methylene group to either N-(2-aminoethyl)-beta-alanine or N-(3-aminopropyl)glycine were prepared. Alternatively, the linker to the nucleobase was extended from methylenecarbonyl to ethylenecarbonyl. The thermal stability of the hybrids between these PNA oligomers and complementary DNA oligonucleotides was significantly lower than that of the corresponding complexes involving unmodified PNA. However, the sequence selectivity was retained. Thymidyl decamers with all N-(2-aminoethyl)-beta-alanine or N-(3-aminopropyl)glycine backbones were prepared and shown to be unable to hybridize to the complementary (dA)(10) oligonucleotides, whereas a PNA decamer containing only ethylenecarbonyl linkers between the nucleobases and the N-(2-aminoethyl)glycine backbone showed weak but sequence-specific affinity for complementary DNA. All hybrids involving homopyrimidine PNA oligomers exhibited (PNA)(2)/DNA stoichiometry, whereas mixed-sequence PNA oligomers formed PNA/DNA duplexes. The preferred binding direction between the modified PNA and DNA in the duplex motifs was antiparallel, as previously reported for complexes involving unmodified PNA.
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| 7. |
- 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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| 8. |
- Koch, T., et al.
(författare)
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PNA-Peptide Chimerae
- 1995
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Ingår i: Tetrahedron Letters. - 0040-4039 .- 1873-3581. ; 36:38, s. 6933-6936
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Tidskriftsartikel (refereegranskat)abstract
- Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.
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| 9. |
- Lagriffoule, P., et al.
(författare)
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Peptide nucleic acids with a conformationally constrained chiral cyclohexyl-derived backbone
- 1997
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Ingår i: Chemistry - A European Journal. - 1521-3765 .- 0947-6539. ; 3:6, s. 912-919
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Tidskriftsartikel (refereegranskat)abstract
- Peptide nucleic acid (PNA) is an achiral nucleic acid mimic with a backbone consisting of partly flexible amino-ethyl glycine units. By replacing the aminoethyl portion of the backbone by an amino cyclohexyl moiety, either in the (S,S) or the (R,R) configuration, we have synthesized conformationally constrained PNA residues. PNA oligomers containing (S,S)-cyclohexyl residues were able to form hybrid complexes with DNA or RNA, with little effect on the thermal stability (Delta T-m = +/- 1 degrees C per (S,S) unit, depending on their number and the sequence). In contrast, incorporation of the (R,R) isomer resulted in a drastic decrease in the stability of the PNA-DNA (or RNA) complex (Delta T-m = -8 degrees C per (R,R) unit). In PNA-PNA duplexes, however, the (R,R)- and (S,S)-cyclohexyl residues only exerted a minor effect on the stability, and the complexes formed with the two isomers are of opposite handedness, as evidenced from circular dichroism spectroscopy. In some cases the introduction of a single (S,S) residue in a PNA 15-mer improves its sequence specificity for DNA or RNA. From the thermal stabilities and molecular modeling based on the solution structure of a PNA-DNA duplex determined by NMR techniques, we conclude that the right-handed helix can accommodate the (SIS) isomer more easily than the (R,R) isomer. Thermodynamic measurements of Delta H and Delta S upon PNA-DNA duplex formation show that the introduction of an (S,S)-cyclohexyl unit in the PNA does indeed decrease the entropy loss, indicating a more conformationally constrained structure. However, the more favorable entropic contribution is balanced by a reduced enthalpic gain, indicating that the structure constrained by the cyclohexyl group is not so well suited for DNA hybridization.
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| 10. |
- Leijon, M., et al.
(författare)
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STRUCTURAL CHARACTERIZATION OF PNA-DNA DUPLEXES BY NMR - EVIDENCE FOR DNA IN A B-LIKE CONFORMATION
- 1994
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 33:33, s. 9820-9825
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Tidskriftsartikel (refereegranskat)abstract
- The nucleic acid analogues PNA (peptide nucleic acids) hybridize with DNA of complementary sequence. The solution structures of two PNA-DNA duplexes, H-(GCTATGTC)-NH2.d(GACATAGC) and H-(GTAGATCACT)-NH2.d(AGTGATCTAC), have been studied by H-1 NMR. It was found that the PNA-DNA hybrids are base paired by hydrogen bonds, most likely of the Watson-Crick type. From two-dimensional NOESY and COSY results it is concluded that the DNA strand in the PNA-DNA complex adopts a B-like structure with the deoxyribose sugars in the C2'-endo conformation.
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