Total chemical synthesis and biophysical properties of a designed soluble 24 kDa amyloid analogue†,Chemical Science

当前位置： X-MOL 学术 › Chem. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Total chemical synthesis and biophysical properties of a designed soluble 24 kDa amyloid analogue†
Chemical Science ( IF 7.6 ) Pub Date : 2018-05-25 00:00:00 , DOI: 10.1039/c8sc01790e
Régis Boehringer _{1,

2,

3,

4,

5} , Bruno Kieffer _{3,

6,

7,

8,

9} , Vladimir Torbeev _{1,

2,

3,

4,

5}

Affiliation

Discovering molecular probes that specifically recognize distinct amyloid structures is highly important for physiological studies of protein-misfolding diseases as well as for the development of diagnostic reagents and inhibitors of amyloid self-assembly. Here, we demonstrate an approach that allows for identification of N-methylated peptides that are specific binders for a particular amyloid fiber subtype (or polymorph). Protein design and chemical synthesis were used to produce covalently tethered amyloid analogues with molecular masses approaching 24 kDa and containing nine copies of an amyloidogenic peptide. Such engineered constructs served as a molecular testing platform to evaluate the aggregation properties and solubility as a function of N-methylation pattern. An advantage of the method is the possibility of biophysical characterization of amyloid constructs in solution.

中文翻译：

设计的可溶性24 kDa淀粉样类似物的总化学合成和生物物理特性†

发现能特异性识别不同淀粉样蛋白结构的分子探针对于蛋白质错误折叠疾病的生理研究以及淀粉样蛋白自组装诊断试剂和抑制剂的开发非常重要。在这里，我们演示了一种方法，该方法可以识别N-甲基化的肽，N-甲基化的肽是特定淀粉样蛋白纤维亚型（或多晶型物）的特异性结合剂。蛋白设计和化学合成被用于生产具有接近24 kDa的分子质量并包含九个淀粉样蛋白生成肽拷贝的共价束缚的淀粉样蛋白类似物。这种工程化的构建体充当了分子测试平台，以评估聚集性质和溶解度与氮的函数关系。-甲基化模式。该方法的优点是可以对溶液中的淀粉样蛋白构建物进行生物物理表征。

更新日期：2018-05-25

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11