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生理条件下酚类化合物对人溶菌酶原纤维形成的影响:抑制还是促进?

Impact of Phenolic Compounds on Fibrillogenesis of Human Lysozyme under Physiological Conditions: Inhibition or Promotion?

作者信息

López Santos, Rojo-Domínguez Arturo, Nájera Hugo

机构信息

Posgrado en Ciencias Naturales e Ingeniería, Universidad Autónoma MetropolitanaCuajimalpa, Av. Vasco de Quiroga 4871, Colonia Santa Fe Cuajimalpa, Alcaldía Cuajimalpa de Morelos, Ciudad de México 05348, Mexico.

Departamento de Ciencias Naturales, Universidad Autónoma MetropolitanaCuajimalpa, Av. Vasco de Quiroga 4871, Colonia Santa Fe Cuajimalpa, Alcaldía Cuajimalpa de Morelos, Ciudad de México 05348, Mexico.

出版信息

ACS Omega. 2025 Aug 5;10(32):35842-35849. doi: 10.1021/acsomega.5c02787. eCollection 2025 Aug 19.

Abstract

Numerous compounds have been studied in the search for a potential drug to interrupt the process of formation of the amyloid fibers. Human lysozyme is a good model for studying the formation of amyloid fibers. In this research, the effect of phenolic compounds (caffeic acid, l-tyrosine, pyrogallol, guaiacol, 6-(-toluidino)-2-naphthalenesulfonic, epicatechin, chrysin, quercetin) during the formation of amyloid fibers at physiological conditions (37 °C and pH 7.5) was studied, resulting in inhibition with certain compounds; on the contrary, the formation of fibers was favored by others. Fluorescence experiments were carried out, like thioflavin T and 8-anilino-1-naphthalenesulfonic acid, where the signal change indicates an increase or a decrease of the amyloid fibers. Circular dichroism was made to understand the changes in the second structure produced for the interaction of the phenolic compounds with the lysozyme. Additionally, molecular docking experiments indicate that the interaction of the compounds with specific amino acids of lysozyme is crucial for inhibiting or exerting a higher effect on fiber formation.

摘要

为了寻找一种能够阻断淀粉样纤维形成过程的潜在药物,人们对众多化合物进行了研究。人溶菌酶是研究淀粉样纤维形成的良好模型。在本研究中,考察了酚类化合物(咖啡酸、L-酪氨酸、连苯三酚、愈创木酚、6-(对甲苯胺基)-2-萘磺酸、表儿茶素、白杨素、槲皮素)在生理条件(37℃和pH 7.5)下对淀粉样纤维形成过程的影响,结果发现某些化合物具有抑制作用;相反,其他一些化合物则有利于纤维的形成。进行了荧光实验,如使用硫黄素T和8-苯胺基-1-萘磺酸,信号变化表明淀粉样纤维的增加或减少。通过圆二色性分析来了解酚类化合物与溶菌酶相互作用所导致的二级结构变化。此外,分子对接实验表明,化合物与溶菌酶特定氨基酸的相互作用对于抑制或增强纤维形成作用至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d59c/12368641/a7b051a8a7a4/ao5c02787_0001.jpg

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