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论文类型：期刊论文

发表刊物：ACS Biomaterials Science & Engineering

收录刊物：SCI

卷号：5

期号：2

页面范围：1092-1099

ISSN号：2373-9878

DOI码：10.1021/acsbiomaterials.8b01384

发表时间：2019-05-01

影响因子：4.511

摘要：Misfolding and amyloid formation of human islet amyloid polypeptide (IAPP) are believed to be critical in the pathogenesis of type 2 diabetes. Inhibitors that can effectively prevent protein aggregation and fibrillation are considered as potential therapeutics for the prevention and treatment of type 2 diabetes. Here, we report that oligotyrosines manipulate IAPP amyloid formation in vitro and modulate IAPP-induced cytotoxicity in a manner that is related to the number of tyrosine units. Tyr2 and Tyr3 can effectively inhibit the aggregation of IAPP, either in bulk solution or in the presence of lipid membranes, and alleviate IAPP-mediated cytotoxicity. On the contrary, Tyr, Tyr4, and Tyr6 do not show significant inhibitory effects on the IAPP aggregation at the same conditions. To the best of our knowledge, this is the first report of a residue-number-dependent inhibition of IAPP aggregation by oligotyrosines, and Tyr2 and Tyr3 are proved to be potent inhibitors of IAPP amyloid formation. The interactions between oligotyrosines and IAPP were simulated through molecular docking, which provides us a new insight about the inhibition mechanism of IAPP amyloid formation that will be helpful for developing antidiabetic drug candidates.

发布期刊链接：https://pubs.acs.org/doi/10.1021/acsbiomaterials.8b01384