Effect of a Short Peptide with Alternating L-and D-Amino Acid on the Aggregation and Membrane Damage of hIAPP  

作　　者：MENG Feihong WANG Yajie LU Tong WANG Chunyu LI Fei 

机构地区：[1]State Key Laboratory of Supramolecular Structure and Materials,Jilin University,Changchun,130012,P.R.China

出　　处：《Chemical Research in Chinese Universities》2021年第3期787-794,共8页高等学校化学研究（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.21673099).

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.

关 键 词：Alpha-sheet Amyloid peptide TOXICITY 

分 类 号：O62[理学—有机化学]