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-NH2 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-NH2 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.
Keywords: SPPS; aggregation; amylin; amyloid-like fiber formation; diabetes; self-assembling; triazine coupling reagent.
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