寻找负责人类胰岛素聚集的 A (13-19) 和 B (12-17) 片段最短片段。
The quest for the shortest fragments of A (13-19) and B (12-17) responsible for the aggregation of human insulin.
机构信息
Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
Institute of General Food Chemistry, Faculty of Biotechnology & Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland.
出版信息
Nanomedicine (Lond). 2016 Aug;11(16):2083-101. doi: 10.2217/nnm-2016-0100. Epub 2016 Jul 27.
AIM
To identify the shortest components of A13-A19, B12-B17 fragments capable for fibrillation and to validate the dependability of aggregation on the presence of hydroxyl group engaged in the 'tyrosine kissing'.
MATERIALS & METHODS: Fragments A13-A19 and B12-B17 of insulin and all shortened analogues were obtained by using DMT/NMM/TosO(-) as a coupling reagent. The aggregation was studied by three independent tests.
RESULTS
Studies on the susceptibility to aggregation of truncated analogs of insulin amyloidogenic core show three groups of peptides.
CONCLUSION
Truncation of A13-A419 fragment shows that fibrous structures are formed by all peptides bearing (13)H-LeuTyr-OH(14). Propensity to aggregation was found for (16)H-TyrLeu-OH(17) B12-B17 fragment. Tyrosine residue modification by incorporation of tert-butyl group on hydroxyl function gave analogues still predisposed to aggregation.
目的
确定 A13-A19、B12-B17 片段中具有纤维形成能力的最短片段，并验证羟基参与“酪氨酸亲吻”对聚集的依赖性。
材料与方法
使用 DMT/NMM/TosO(-)作为偶联试剂，获得胰岛素的 A13-A19 和 B12-B17 片段及所有缩短的类似物。通过三种独立的试验研究聚集情况。
结果
对胰岛素淀粉样核心的截断类似物的聚集易感性研究表明存在三组肽。
结论
A13-A419 片段的截断表明，所有带有（13）H-LeuTyr-OH(14)的肽都形成纤维结构。发现 B12-B17 片段的（16）H-TyrLeu-OH(17)具有聚集倾向。通过在羟基上引入叔丁基对酪氨酸残基进行修饰，得到的类似物仍然容易聚集。
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