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Thyroxine metabolite-derived 3-iodothyronamine (T1AM) and synthetic analogs as efficient suppressors of transthyretin amyloidosis

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Title
Thyroxine metabolite-derived 3-iodothyronamine (T1AM) and synthetic analogs as efficient suppressors of transthyretin amyloidosis
Author(s)
Kim, Bokyung; Young Ho Ko; Si, Jinbeom; Na, Jongbum; Ortore, Gabriella; Chiellini, Grazia; Kim, Jin Hae
Publication Date
2023-10
Journal
Computational and Structural Biotechnology Journal, v.21, pp.4717 - 4728
Publisher
Research Network of Computational and Structural Biotechnology
Abstract
Aggregation and fibrillization of transthyretin (TTR) is a fatal pathogenic process that can cause cardiomyopathic and polyneuropathic diseases in humans. Although several therapeutic strategies have been designed to prevent and treat related pathological events, there is still an urgent need to develop better strategies to improve potency and wider applicability. Here, we present our study demonstrating that 3-iodothyronamine (T1AM) and selected thyronamine-like compounds can effectively prevent TTR aggregation. T1AM is one of the thyroid hormone (TH) metabolites, and T1AM and its analogs, such as SG2, SG6, and SG12, are notable molecules for their beneficial activities against metabolic disorders and neurodegeneration. Using nuclear magnetic resonance (NMR) spectroscopy and biochemical analysis, we confirmed that T1AM analogs could bind to and suppress acid-induced aggregation of TTR. In addition, we employed computational approaches to further understand the detailed mechanisms of the interaction between T1AM analogs and TTR. This study demonstrates that T1AM analogs, whose beneficial effects against several pathological processes have already been proven, may have additional benefits against TTR aggregation and fibrillization. Moreover, we believe that our work provides invaluable insights to enhance the pleiotropic activity of T1AM and structurally related analogs, relevant for their therapeutic potential, with particular reference to the ability to prevent TTR aggregation. © 2023 The Authors
URI
https://pr.ibs.re.kr/handle/8788114/14213
DOI
10.1016/j.csbj.2023.09.028
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > 1. Journal Papers (저널논문)
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