Indexed by:Journal paper

Journal:ACS Biomaterials Science & Engineering

Included Journals:SCI

Volume:5

Issue:2

Page Number:1092-1099

ISSN No.:2373-9878

DOI number:10.1021/acsbiomaterials.8b01384

Date of Publication:2019-05-01

Impact Factor:4.511

Abstract: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.

Links to published journals:https://pubs.acs.org/doi/10.1021/acsbiomaterials.8b01384