A Fluorogenic Molecule for Probing Islet Amyloid Using Flavonoid as a Scaffold Design

Wei Ling Chen, Shih Ting Ma, Yun Wen Chen, Yen Cheng Chao, Ai Ci Chan, Ling Hsien Tu, Wei Min Liu

研究成果: 雜誌貢獻文章

摘要

Aggregation of polypeptides and proteins is commonly associated with human and other vertebrate diseases. For example, amyloid plaques consisting of amyloid-β proteins are frequently identified in Alzheimer's disease and islet amyloid formed by islet amyloid polypeptide (IAPP, amylin) can be found in most patients with type 2 diabetes (T2D). Although many fluorescent dyes have been developed to stain amyloid fibrils, very few examples have been designed for IAPP. In this study, a series of environmentally sensitive fluorescent probes using flavonoid as a scaffold design are rationally designed and synthesized. One of these probes, namely 3-HF-ene-4′-OMe, can bind to IAPP fibrils but not nonfibrillar IAPP by exhibiting a much stronger fluorescent enhancement at 535 nm. In addition, this probe shows better detection sensitivity to IAPP fibrils compared with that of conventionally used thioflavin-T. We demonstrate that 3-HF-ene-4′-OMe can be used to monitor the kinetics of IAPP fibril formation in vitro even in the presence an amyloid inhibitor. To test the specificity of the probe, we attempt to incubate this probe with amyloid fibrils formed from other amyloidogenic proteins. Interestingly, this probe shows different responses when mixed with these fibrils, suggesting the mode of binding of this probe on these fibrils could be different. Moreover, we show that this probe is not toxic to pancreatic mouse β-cells. Further structural optimization based on the structure of 3-HF-ene-4′-OMe may yield a specific probe for imaging islet amyloid in the pancreas. That would improve our understanding of the relationship between islet amyloid and T2D.

原文英語
頁(從 - 到)1482-1492
頁數11
期刊Biochemistry
59
發行號15
DOIs
出版狀態已發佈 - 2020 四月 21

ASJC Scopus subject areas

  • Biochemistry

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  • 引用此

    Chen, W. L., Ma, S. T., Chen, Y. W., Chao, Y. C., Chan, A. C., Tu, L. H., & Liu, W. M. (2020). A Fluorogenic Molecule for Probing Islet Amyloid Using Flavonoid as a Scaffold Design. Biochemistry, 59(15), 1482-1492. https://doi.org/10.1021/acs.biochem.0c00076