关键词: aggregation amyloid β peptide homotaurine liposomes marine drugs κ-carrageenan

Mesh : Liposomes / chemistry Carrageenan / chemistry Amyloid beta-Peptides / chemistry Taurine / chemistry analogs & derivatives Kinetics Peptide Fragments / chemistry Particle Size Protein Aggregates

来  源:   DOI:10.3390/molecules29153460   PDF(Pubmed)

Abstract:
The kinetics of amyloid aggregation was studied indirectly by monitoring the changes in the polydispersity of mixed dispersion of amyloid β peptide (1-40) and composite liposomes. The liposomes were prepared from the 1,2-dioleoyl-sn-glicero-3-phoshocholine (DOPC) phospholipid and stabilised by the electrostatic adsorption of κ-carrageenan. The produced homotaurine-loaded and unloaded liposomes had a highly negative electrokinetic potential and remarkable stability in phosphate buffer (pH 4 and 7.4). For the first time, the appearance and evolution of the aggregation of Aβ were presented through the variation in the standard percentile readings (D10, D50, and D90) obtained from the particle size distribution analysis. The kinetic experiments indicated the appearance of the first aggregates almost 30 min after mixing the liposomes and peptide solution. It was observed that by adding unloaded liposomes, the size of 90% of the particles in the dispersion (D90) increased. In contrast, the addition of homotaurine-loaded liposomes had almost minimal impact on the size of the fractions of larger particles during the kinetic experiments. Despite the specific bioactivity of homotaurine in the presence of natural cell membranes, this study reported an additional inhibitory effect of the compound on the amyloid peptide aggregation due to the charge effects and \'molecular crowding\'.
摘要:
通过监测淀粉样蛋白β肽(1-40)和复合脂质体的混合分散体多分散性的变化,间接研究了淀粉样蛋白聚集的动力学。脂质体由1,2-二油酰基-sn-glicero-3-磷胆碱(DOPC)磷脂制备,并通过κ-角叉菜胶的静电吸附稳定。所产生的装载和卸载的高牛磺酸的脂质体在磷酸盐缓冲液(pH4和7.4)中具有高度负的电动电势和显着的稳定性。第一次,Aβ聚集的出现和演变通过从粒度分布分析获得的标准百分位数读数(D10,D50和D90)的变化来呈现。动力学实验表明在混合脂质体和肽溶液后几乎30分钟出现第一聚集体。观察到通过添加未加载的脂质体,分散体中90%的颗粒的尺寸(D90)增加。相比之下,在动力学实验过程中,添加负载高牛磺酸的脂质体对较大颗粒级分的大小影响几乎最小.尽管高牛磺酸在天然细胞膜的存在下具有特定的生物活性,这项研究报道,由于电荷效应和“分子拥挤”,该化合物对淀粉样肽聚集有额外的抑制作用。
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