Formation of spherulitic amyloid ß aggregate by anionic liposomes.

Alzheimer's disease is the most common form of senile dementia. This neurodegenerative disorder is characterized by an amyloid deposition in senile plaques, composed primarily of fibrils of an aggregated peptide, amyloid ß (Aß). The modeling of a senile plaque formation on a model neuronal membrane under the physiological condition is an attractive issue. In this study, we used anionic liposomes to model the senile plaque formation by Aß. The growth behavior of amyloid Aß fibrils was directly observed, revealing that the induction of the spherulitic Aß aggregates could result from the growth of seeds in the presence of anionic liposomes. The seeds of Aß fibrils strongly interacted with negatively charged liposome and the subsequent association of the seeds were induced to form the seed cluster with many growth ends, which is advantageous for the formation of spherulitic Aß aggregates. Therefore, anionic liposomes mediated not only fibril growth but also the aggregation process. These results imply that anionic liposome membranes would affect the aggregate form of Aß fibrils. The modeling of senile plaque reported here is considered to have great potential for study on the amyloidosis.

A bridged nucleic acid, 2',4'-BNA COC: synthesis of fully modified oligonucleotides bearing thymine, 5-methylcytosine, adenine and guanine 2',4'-BNA COC monomers and RNA-selective nucleic-acid recognition.

Recently, we synthesized pyrimidine derivatives of the 2'-O,4'-C-methylenoxymethylene-bridged nucleic-acid (2',4'-BNA(COC)) monomer, the sugar conformation of which is restricted in N-type conformation by a seven-membered bridged structure. Oligonucleotides (BNA(COC)) containing this monomer show high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation. Here, BNA(COC) consisting of 2',4'-BNA(COC) monomers bearing all four bases, namely thymine, 5-methylcytosine, adenine and guanine was efficiently synthesized and properties of duplexes containing the 2',4'-BNA(COC) monomers were investigated by UV melting experiments and circular dichroism (CD) spectroscopy. The UV melting curve analyses showed that the BNA(COC)/BNA(COC) duplex possessed excellent thermal stability and that the BNA(COC) increased thermal stability with a complementary RNA strand. On the other hand, BNA(COC)/DNA heteroduplexes showed almost the same thermal stability as RNA/DNA heteroduplexes. Furthermore, mismatched sequence studies showed that BNA(COC) generally improved the sequence selectivity with Watson-Crick base-pairing compared to the corresponding natural DNA and RNA. A CD spectroscopic analysis indicated that the BNA(COC) formed duplexes with complementary DNA and RNA in a manner similar to natural RNA.

Morphological changes in vesicles and release of an encapsulated compound triggered by a photoresponsive Malachite Green leuconitrile derivative.

Photoinduced morphological changes in phosphatidylcholine vesicles are triggered by a Malachite Green leuconitrile derivative dissolved in the lipidic membrane, and are observed at Malachite Green derivative/lipid ratios <5 mol %. This Malachite Green derivative is a photoresponsive compound that undergoes ionization to afford a positive charge on the molecule by UV irradiation. The Malachite Green derivative exhibits amphiphilicity when ionized photochemically, whereas it behaves as a lipophilic compound under dark conditions. Cryo-transmission electron microscopy was used to determine vesicle morphology. The effects of the Malachite Green derivative on vesicles were studied by dynamic light scattering and fluorescence resonance energy transfer. Irradiation of vesicles containing the Malachite Green derivative induces nonspherical vesicle morphology, fusion of vesicles, and membrane solubilization, depending on conditions. Furthermore, irradiation of the Malachite Green derivative induces the release of a vesicle-encapsulated compound.

Novel bis(ethylenedithio)tetrathiafulvalene-based organic conductor with 1,1'-ferrocenedisulfonate.

A new bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF)-based salt with a ferrocenyl moiety, alpha' ''-(BEDT-TTF)(4)(Fe(C(5)H(4)SO(3))(2)).6H(2)O, has been prepared. The ferrocenyl part of this salt is neutral and diamagnetic, but the magnetic susceptibility is well modeled by a Curie-Weiss law with C = 0.142 emu.K.mol(-1) (approximately 1/3 of s = 1/2 spin). The spin is likely to be localized on the donor layer because of its unique charge disproportionation.

Synthesis of 2',4'-BNACOC bearing a purine nucleobase.

Recently, we have synthesized pyrimidine derivatives of 2',4'-BNA(COC) monomer, the sugar conformation of which was restricted in N-form by a seven-membered bridged structure. The oligonucleotides containing these monomers showed high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation. For an application to antisense methodology, it is important to synthesize 2',4'-BNA(COC) monomers bearing a purine nucleobase. However, the formation of methyleneoxymethylene (COC) linkage in the purine derivatives failed under the acidic conditions used for the synthesis of 2',4'-BNA(COC) with pyrimidine nucleobases. After several examinations, we successfully achieved the synthesis of 2',4'-BNA(COC) monomers bearing a purine nucleobase via the formation of COC linkage using Pummerer-type reaction.

Synthesis and properties of 2'-O,4'-C-methyleneoxymethylene bridged nucleic acid.

A novel bridged nucleic acid (BNA) analogue, 2'-O,4'-C-methyleneoxymethylene bridged nucleic acid (2',4'-BNA(COC)), was synthesized and incorporated into oligonucleotides. The 2',4'-BNA(COC) modified oligonucleotides showed high binding affinity with an RNA complement and significant enzymatic stability against snake venom phosphodiesterase.