Design and synthesis of new trehalose-conjugated pentapeptides as inhibitors of Aβ(1-42) fibrillogenesis and toxicity
Design and synthesis of new trehalose-conjugated pentapeptides as inhibitors of Aβ(1-42) fibrillogenesis and toxicity
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DOI：
10.1002/psc.1109
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发表时间：
2009-03-01
影响因子：
2.1
通讯作者：
Rizzarelli, Enrico
中科院分区：
文献类型：
--
作者：
De Bona, Paolo;Giuffrida, Maria Laura;Rizzarelli, Enrico
淀粉样蛋白Aβ多肽的聚集及其积聚成不溶性沉积物(斑块)被认为是阿尔茨海默病(AD)相关神经元功能障碍的主要原因；因此，可以干扰Aβ淀粉样蛋白纤维形成的小分子对潜在的治疗策略感兴趣。合成了三个新的海藻糖结合多肽--β-折叠肽IA-β5p。二糖共价连接到LPFFD多肽链的不同位置，即N-末端、C-末端或天冬氨酸侧链。用不同溶剂中的圆二色谱评价了这些化合物的多肽构象的变化。分别用荧光分析和动态扫描力显微镜研究了这些糖肽对Aβ聚集体自组装和形态的影响。所有合成的化合物都被测试为Aβ毒性的拮抗剂，对纯培养的大鼠皮质神经元具有抑制作用。版权所有(C)2009欧洲肽协会和John Wiley&Sons，Ltd.
Aggregation of the amyloid A beta peptide and its accumulation into insoluble deposits (plaques) are believed to be the main cause of neuronal dysfunction associated with Alzheimer's disease (AD); small molecules that can interfere with the A beta amyloid fibril formation are therefore of interest for a potential therapeutic strategy. Three new trehalose-conjugated peptides of the well known beta-sheet breaker peptide iA beta 5p, were synthesized. The disaccharide was covalently attached to different sites of the LPFFD peptide chain, i.e. at the N-terminus, C-terminus or at the Asp side chain. CD spectroscopy in different solvents was used to assess changes in the peptide conformation of these compounds. The effects of these glycopeptides on the self-assembly and morphology of A beta aggregates were investigated by ThT fluorescence assay and dynamic Scanning Force Microscopy, respectively. All the synthesized compounds were tested as inhibitors of A beta toxicity toward pure cultures of rat cortical neurons. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.