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Tetracycline derivatives resist the assembly behavior of human islet amyloid polypeptide.
Xu, Jufei; Zhao, Cong; Huang, Xiangyi; Du, Weihong.
Afiliación
  • Xu J; Department of Chemistry, Renmin University of China, Beijing, 100872, China.
  • Zhao C; Department of Chemistry, Renmin University of China, Beijing, 100872, China.
  • Huang X; Department of Chemistry, Renmin University of China, Beijing, 100872, China.
  • Du W; Department of Chemistry, Renmin University of China, Beijing, 100872, China. Electronic address: whdu@ruc.edu.cn.
Biochimie ; 174: 95-106, 2020 Jul.
Article en En | MEDLINE | ID: mdl-32330570
The misfolding of amyloid proteins is closely correlated with the pathogenesis of protein conformation-related diseases, such as Alzheimer's disease (AD), prion disease, and type 2 diabetes mellitus (T2DM). The deposition of human islet amyloid polypeptide (hIAPP) and amyloid-ß (Aß) protein is entangled in AD and diabetes mellitus. The development of potential inhibitors is a feasible therapeutic strategy to treat these diseases by resisting peptide aggregation. Doxycycline is a typical clinical antibiotic that has been utilized in neurodegenerative studies. However, the roles of tetracyclines in hIAPP aggregation remain unclear. Herein, we studied the inhibitory effects of three tetracycline derivatives, namely, minocycline hydrochloride (1), methacycline hydrochloride (2), and doxycycline (3), on the fibril formation and cytotoxicity of hIAPP and compared with that of Aß. The well-known 3 was selected and compared with 1 and 2. Tetracycline derivatives acted as effective inhibitors to reverse the self-assembly of hIAPP and Aß, and disaggregate the aged peptides fibrils into mostly monomers. Tetracycline derivatives also reduced the cytotoxicity induced by amyloid peptide oligomerization. Further molecular mechanism studies revealed hydrophobic and hydrogen bond interactions as the primary binding pattern between tetracycline derivatives and peptides. A good bioactivity against amyloidosis was demonstrated by three tetracyclines. This work provided a basis for using tetracycline antibiotics as potential inhibitors against hIAPP aggregation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tetraciclina / Péptidos beta-Amiloides / Polipéptido Amiloide de los Islotes Pancreáticos / Agregación Patológica de Proteínas Límite: Humans Idioma: En Revista: Biochimie Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tetraciclina / Péptidos beta-Amiloides / Polipéptido Amiloide de los Islotes Pancreáticos / Agregación Patológica de Proteínas Límite: Humans Idioma: En Revista: Biochimie Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia