通过同电点调节对蛋白质溶解度进行光控制
Karthik Nadendla1, Simon H Friedman1
1Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City , Kansas City, Missouri 64108, United States.
Journal of the American Chemical Society
|December 2, 2017
概括
这项研究引入了一种无聚合物方法,用于光控制的胰岛素释放. 修改后的胰岛素在皮肤pH下沉,在照射时释放原生胰岛素,改善治疗储存材料.
科学领域:
- 生物材料科学
- 药物输送系统
- 蛋白质工程
背景情况:
- 使用光激活储存 (PAD) 方法控制蛋白质释放,使用光诱导的溶解性变化.
- 传统的基于聚合物的PAD系统面临着材料效率低下和聚合物清除的挑战.
研究的目的:
- 开发无聚合物光激活储存器以释放治疗性蛋白质.
- 通过光诱导的同电点和可溶性转移来控制胰岛素储存.
主要方法:
- 通过光裂链接器将基团与胰岛素连接起来,以改变其同电点 (pI).
- 合成和特征改造的胰岛素与转移的PI值.
- 在实验室中评估仓库形成,蛋白质释放动力学和物质清除.
主要成果:
- 合成了四种经过修改的胰岛素,其PI值发生了变化,使其能够在生理pH值下沉.
- 在pH 4时显示P2胰岛素的溶解性,在pH 7. 2时显示沉性.
- 照射会以第一阶段的动态方式释放出原生可溶性胰岛素,留下可吸收的小分子.
结论:
- 已成功开发出无聚合物光激活的胰岛素释放储存器.
- 这种方法利用光诱导的PI转移来控制蛋白质溶解度和储存形成.
- 这些材料为光激活治疗提供了改进,高效和潜在的理想平台.
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