摘要
Alpha-sheet is believed to be a significant structural compo-nent,formed in the fibrillation process of the amyloid pep-tide.However,the knowledge about the role of a-sheet played in the amyloidosis and toxicity is lack.In this work,we modi-fied a short peptide derived from the core region of human islet amyloid polypetide(hIAPP,hIAPP18-27)with an alternating D-amino acid replacement and investigated the effects of the L/D alternating peptide on the fibrillar aggregation and the membrane damage of hIAPP using NMR,ThT fluorescence assay,circular dichroism(CD),transmission electron microscopy(TEM)and leakage assay,and com-pared the results with those of hIAPP_(18-27) without D-amino acid re-placement.We show that the short peptide with alternating L-and D-amino acids forms an a-sheet structure and is more potent in pro-moting the fibrillation of hIAPP and reducing the ability of hIAPP to disrupt the membrane composed of POPG and POPC[1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine]1:4 lipids than the short pep-tide with all L-amino acids in a random coil structure.The higher po-tency of the D/L alternating peptide in these activities is attributed to its ability to induce the a-sheet-like structure in the core region of hIAPP and block the interaction of hIAPP with the membrane more effectively.
基金
This work was supported by the National Natural Science Foundation of China(No.21673099).