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Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20
Author(s) -
Mao Yexuan,
Yu Lanlan,
Mao Mengfan,
Ma Chuanguo,
Qu Lingbo
Publication year - 2018
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3058
Subject(s) - lipopeptide , microscale thermophoresis , amyloid (mycology) , chemistry , thioflavin , islet , biochemistry , peptide , biophysics , amyloid disease , fibril , amyloid fibril , bacteria , diabetes mellitus , amyloid β , biology , medicine , disease , endocrinology , inorganic chemistry , genetics , alzheimer's disease
Type 2 diabetes mellitus, a kind of conformational disease, has become an epidemic disease, which seriously endangers the quality of life and health of human beings. The deposition of human islet amyloid polypeptide (hIAPP) has been considered as one of the major pathological features of type 2 diabetes mellitus. As lipopeptides have some hydrophobic groups, which are similar to the reported aggregation inhibitors, and some lipopeptides could prevent cells from depositing of amyloid fibrils, several potential lipopeptide inhibitors have been engineered and synthesized, which have been assessed for their inhibitory effect in preventing amyloid fibrils formation of hIAPP 11‐20 by using the conventional thioflavin‐T fluorescence assay and new technique microscale thermophoresis (MST). The final amyloid fibrils of hIAPP 11‐20 were characterized by transmission electron microscopy. Results suggested that with the increasing length of alkyl chain, the antiaggregation efficiency of lipopeptide inhibitors towards hIAPP 11‐20 increased gradually. Meanwhile, the amount of arginines, which represent the head groups of lipopeptides, may also have some influence. The binding events also showed that the inhibitory efficiency of these lipopeptide inhibitors was enhanced with the increase of affinities between lipopeptides and hIAPP 11‐20 , which were obtained from MST. This study demonstrated the efficiency of lipopeptides in inhibiting the aggregation of hIAPP 11‐20 and proved that MST could be regarded as an appropriate and rapid method to screen potential inhibitors of hIAPP 11‐20 or other amyloid proteins. This study also broadens the types of inhibitors on inhibiting amyloid formation of hIAPP.