Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, Lodz, 90-924, Poland.
Institute of Applied Computer Science, Lodz University of Technology, Stefanowskiego Łódź, 18/22, Lodz, 90-537, Poland.
Chem Biodivers. 2020 Sep;17(9):e2000501. doi: 10.1002/cbdv.202000501. Epub 2020 Sep 8.
Human Islet Amyloid Polypeptide (hIAPP) plays a key role in the pathogenesis of type II diabetes. The aim of this research was to search for new amyloidogenic fragments of hIAPP. An initial attempt to predict the amyloidogenic cores of polypeptides/proteins using five different computer programs did not provide conclusive results. Therefore, we synthesized hIAPP fragments covering the entire hormone. The fragments were assessed for their aggregation ability, using recommended methods to search for the amyloidogenic fragments of the polypeptides/proteins. It was found that fragments (18-22) H-HSSNN-OH and (33-37) H-GSNTY-NH aggregate and form stable amyloid-like structures. Both of these fragments have a much higher antiproliferative activity relative to the RIN-5F cell compared to the (23-27) H-FGAIL-OH fragment widely regarded as the amyloidogenic core of amylin. The analog of (33-37) H-GSNTY-NH containing a free carboxy group on the C-terminal amino acid (H-GSNTY-OH) does not have amyloidogenic properties and can therefore be considered as a potential inhibitor of amylin aggregation. Research on the use of non-aggregating amylin fragments as potential hormone aggregation inhibitors is ongoing.
人胰岛淀粉样多肽（hIAPP）在 2 型糖尿病的发病机制中起关键作用。本研究旨在寻找 hIAPP 的新淀粉样肽片段。使用五个不同的计算机程序对多肽/蛋白质的淀粉样核心进行初步预测，并未得出明确的结果。因此，我们合成了覆盖整个激素的 hIAPP 片段。使用推荐的方法评估了这些片段的聚集能力，以寻找多肽/蛋白质的淀粉样肽片段。结果发现，片段（18-22）H-HSSNN-OH 和（33-37）H-GSNTY-NH 聚集并形成稳定的类淀粉样结构。与被广泛认为是胰岛淀粉样肽核心的（23-27）H-FGAIL-OH 片段相比，这两个片段对 RIN-5F 细胞都具有更高的抗增殖活性。含有游离羧基的（33-37）H-GSNTY-NH 的类似物（H-GSNTY-OH）没有淀粉样性质，因此可以被认为是胰岛淀粉样肽聚集的潜在抑制剂。关于使用非聚集性胰岛淀粉样肽片段作为潜在激素聚集抑制剂的研究正在进行中。
