用于选择性输送生物活性的定制可逆拼接
Zizhen Zeng1, Jibao Zhu1, Xiaoyu Deng2
1National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, P. R. China.
Journal of the American Chemical Society
|December 19, 2022
概括
这项研究引入了可逆接,以提高稳定性和向性传递. 该方法使用宏循环和触发式脱循环来控制治疗的释放.
科学领域:
- 化学生物学
- 提供药物
- 类治疗药物
背景情况:
- 类药物具有治疗潜力,但在稳定性和向性治疗方面面临挑战.
- 目前的改方法往往缺乏可逆性或对释放的精确控制.
- 开发可控激活和输送的策略对于推进疗法至关重要.
研究的目的:
- 开发一种新的可逆接策略,以提高稳定性和向输送.
- 证明这种策略在细胞内和细胞外递送中的实用性.
- 创建和验证由特定触发器激活的可逆接抗菌 (RStAMPs).
主要方法:
- 开发了一种涉及两个氨基群的宏循环化策略,并通过双重1,4-消除进行脱循环化.
- 概念验证:暂时循环使用素特异性脱甲基酶1 (LSD1) 的抑制剂,以改善细胞膜的透性.
- 设计的RStAMPs具有暂时不稳定的螺旋形状,在感染部位被过氧化 (H2O2) 激活.
主要成果:
- 可逆接增强了的稳定性和细胞膜透,在减少条件下控制细胞内活性的释放.
- 可逆合抗菌 (RStAMPs) 的毒性降低,蛋白酶耐药性增加.
- 在感染部位,RStAMPs被H2O2迅速激活,恢复了螺旋结构和强大的抗菌活性.
结论:
- 这种宏循环化策略为可逆改性和可控输送提供了多功能平台.
- 开发的方法显著提高了的稳定性,生物可用性和向激活.
- 这种方法对在各种医疗应用中推进疗法具有很大的前景,包括抗菌治疗和向癌症治疗.
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