Polyalanine-based peptides as models for self-associated beta-pleated-sheet complexes
Polyalanine-based peptides as models for self-associated beta-pleated-sheet complexes
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DOI：
10.1021/bi963015b
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发表时间：
1997-07-08
期刊：
影响因子：
2.9
通讯作者：
PerezPaya, E
中科院分区：
文献类型：
--
作者：
Blondelle, SE;Forood, B;PerezPaya, E
β-折叠基序在许多神经退行性疾病中的出现使得需要从头设计可溶性模型β-折叠复合物。这样的模型复合物，预计将进一步了解发生从细胞允许的无规卷曲或α-螺旋构象到不溶性细胞有害的β-折叠片基序的相互转换过程。在本研究中，基于聚丙氨酸的肽（即，衍生自Ac-KA（14）K-NH 2），其经历了从单体无规卷曲构象到可溶性大分子β-折叠片层复合物的构象变化，而没有任何共价修饰。相互转换被认为是长度，环境和浓度依赖性和驱动的甲基之间的疏水相互作用的丙氨酸侧链。使用Ac-KA（14）K-NH 2的一系列取代类似物来研究复合物的疏水核心内以及两端的氨基酸可接受性。在许多淀粉样蛋白生成肽中淀粉样蛋白斑块的形成可能与其序列中存在的氨基酸有关，发现这些氨基酸在这些模型β-折叠复合物中具有发生的高倾向。
The occurrence of beta-sheet motifs in a number of neurodegenerative disorders has brought about the need for the de novo design of soluble model beta-sheet complexes. Such model complexes are expected to further the understanding of the interconversion processes that occur from cellular allowed random coil or alpha-helical conformation into insoluble cell-deleterious beta-pleated-sheet motifs. In the present study, polyalanine-based peptides (i.e., derived from Ac-KA(14)K-NH2) were designed that underwent conformational changes from monomeric random coil conformations into soluble, macromolecular beta-pleated-sheet complexes without any covalent modification. The interconversion was found to be length-, environment-, and concentration-dependent and to be driven by hydrophobic interactions between the methyl groups of the alanine side chains. A series of substitution analogs of Ac-KA(14)K-NH2 was used to study the amino acid acceptability within the hydrophobic core of the complex, as well as at both termini. The formation of amyloid plaques in a number of amyloidogenic peptides could be related to the presence of amino acids within their sequences that were found to have a high propensity to occur in these model beta-sheet complexes.