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| 2. |
- DeWeerth, Stephen P., et al.
(författare)
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A Simple Neuron Servo
- 1991
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Ingår i: IEEE Transactions on Neural Networks. - : Institute of Electrical and Electronics Engineers (IEEE). - 1045-9227. ; 2:2, s. 248-251
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- 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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| 5. |
- Hagmar, Per, et al.
(författare)
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IONIC-STRENGTH DEPENDENCE OF THE BINDING OF METHYLENE-BLUE TO CHROMATIN AND CALF THYMUS DNA
- 1992
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Ingår i: Journal of Biomolecular Structure and Dynamics. - 0739-1102 .- 1538-0254. ; 9:4, s. 667-679
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Tidskriftsartikel (refereegranskat)abstract
- The binding of the intercalating dye methylene blue (MB) to chromatin and to free DNA has been studied as a function of ionic strength at very low binding ratios (1 MB/400 DNA bases) using absorption spectroscopy. With increasing salt concentration MB is displaced from chromatin to a higher extent than from DNA. The free energy change for MB binding to chromatin is found to be approximately 5 kJ/mole lower than for binding to DNA. This difference can be explained by the reduced number of high affinity binding sites in chromatin due to the presence of histone proteins. The difference in binding energy is virtually independent of the degree of chromatin condensation and also of the valence of counter ions, suggesting that neither the affinity for, nor the number of intercalation sites in the linker DNA is markedly changed upon the salt-induced condensation. The unaffected thermodynamics of the linker binding suggests that factors such as DNA superhelicity and the electrostatic influence from the chromatosomes remain unchanged during chromatin condensation.
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| 6. |
- Holst, J., et al.
(författare)
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Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis : A comparison with low molecular weight heparin
- 1994
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 71:2, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate whether a truncated recombinant Tissue Factor Pathway Inhibitor (TFPI1-161) which lacked the third Kunitz-type domain and the basic c-terminal region, had an antithrombotic effect comparable to LMWH in a randomised double-dummy study. The experimental thrombosis was induced in jugular veins, in a total of 40 rabbits by a combination of destruction of the endothelium and restricted blood flow. Group 1: placebo, gr 2- LMWH 60 anti-FXa IU/kg, gr 3-5: 0.1, 1.0 and 10.0 mg/kg TFPI1-161. TFPI1-161 reduced the thrombus weights in all treated groups, significantly in doses of 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis and occlusive thrombosis were also significantly reduced in those doses. The antithrombotic properties of TFPI1-161 (1.0-10.0 mg/ kg) measured as thrombus weight, frequency of thrombosis and frequency of occlusive thrombosis was equivalent to the antithrombotic properties of LMWH. In the anti-FXa, APTT and PT-assays TFPI1-161 displayed a dose dependent increase of activity. Recombinant-TFPI1-161 did not influence the anti-FIIa-assay. No haemorrhagic side effects were noted.
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| 7. |
- Holst, J., et al.
(författare)
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Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin(TM)). An experimental investigation in healthy volunteers
- 1994
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235. ; 5:5, s. 795-803
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate whether tinzaparin sodium (a low-molecular-weight heparin (LMWH)) was fully and permanently neutralized in vivo in man by protamine sulphate (PS) after intravenous (i.v.) or subcutaneous (s.c.) injection. Fifty healthy adults equally divided in five age- and sex-matched groups were included. The groups received 50 IU unfractionated heparin (UH)/kg body weight (b.w.) i.v., 50 anti-factor Xa (anti-Xa) IU tinzaparin/kg b.w. i.v., 75 anti-Xa IU tinzaparin/kg b.w. s.c., 175 anti-Xa IU tinzaparin/kg b.w. s.c., or 1 ml of saline s.c. PS was given as a 10 min infusion in a dose of 1 mg/100 IU of heparin in the four first groups while 0.5 mg PS/kg b.w. was given in the placebo group. In the i.v. groups PS was administered 45 min after the heparin injection, and in the s.c. groups 180 min post-heparin injection. In the UH group PS fully and permanently neutralized all three activities. In the i.v. tinzaparin group PS reversed 80% of the anti-Xa activity, while the anti-IIa and aPTT activities were fully reversed. A slight, but statistically significant, increase in anti-Xa and anti-Ila activities were seen following i.v. tinzaparin. In the s.c. groups 60-65% of the observed peak anti-Xa activity was neutralized, anti-IIa was almost completely reversed, and aPTT returned nearly to baseline values. A gradual return of the anti-Xa activity (65-75%), anti-IIa activity (55%) and aPTT activity (35-45%) was seen in the s.c. groups 3 h after reversal compared with the observed peak values. A continuous absorption of tinzaparin from the s.c. depot is presumably the cause of the returned activity. PS caused an 8-27% transient drop in the platelet count in all groups. This study confirms that the anti-Xa activity following i.v. and s.c. administration of tinzaparin (a LMWH) is only partially neutralizable by protamine. This is not due to insufficient dosages of the antidote, as an excess of protamine could be demonstrated ex vivo immediately after the protamine infusion. The present results suggest that protamine neutralization of tinzaparin given s.c. should be obtained with intermittent injections or continuous infusion.
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| 8. |
- 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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| 9. |
- 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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| 10. |
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