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.
The misfolding and aggregation of human islet amyloid polypeptide (IAPP) into β-sheet-enriched amyloid fibrils is linked to type 2 diabetes. Antibodies are potent inhibitors of IAPP amyloidogenesis, but their preparation...
Abstract-As embedded hardware and software become increasingly complex, the traditional command based development debugging operations have been unable to meet the daily needs. Graphical debugging tools have become the most popular choice. As a good open source software, Eclipse provides a large number of expansion nodes for us to develop our own functions. The embedded integrated development environment needs to be integrated with other related software on the basis of Eclipse. This article is to study how Eclipse invokes other software and manages related processes. This article uses the WorkspaceJob class and the Process class provided by Eclipse to complete the related functions.
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