通过移植制备的多 () -蛋白结合物用于ROMP作为PEG的替代品
Elizabathe Davis1, Adam A Caparco1, Nicole F Steinmetz1,2,3,4,5,6
1Department of NanoEngineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Macromolecular bioscience
|September 9, 2023
概括
新的聚氧化 (PONB) 聚合物为生物结合提供了聚乙烯糖醇 (PEG) 的替代品. 这些新型聚合物降低了对生物制剂的免疫反应,解决了对现有的PEGylated治疗方法的担忧.
科学领域:
- 生物结合化学 生物结合化学
- 聚合物科学 聚合物科学
- 免疫学 免疫学 免疫学
背景情况:
- 聚乙烯糖醇 (PEG) 化是改善生物循环时间和降低免疫性的标准.
- 人类中抗PEG抗体的流行率不断增加,这对PEG化治疗药物的安全性构成了挑战.
- 需要使用具有改善免疫特征的替代聚合物.
研究的目的:
- 合成新的氨基胺反应性聚氧化 (PONB) 阻断共聚合物.
- 评估基于PONB的合物 (PONB-PEG和PONB-Zwit) 的蛋白质生物活性和免疫性.
- 将PONB结合物与传统的PEGylated蛋白质进行比较.
主要方法:
- 环开元化聚合 (ROMP) 用于合成PONB块共聚合物.
- 移植到生物结合技术,将聚合物附着在lyszyme (Lyz) 和尿酸氧化酶 (UO) 上.
- 测试以评估结合生物活性和免疫识别.
主要成果:
- 合成的PONB-PEG和PONB-Zwit块共聚合物.
- 利兹-PONB和UO-PONB结合物保留了显著的生物活性.
- 与PEGylated UO相比,UO-PONB结合物显示免疫性降低.
- PONB-Zwit结合物表现出可以忽略不计的PEG特异性免疫识别.
结论:
- 基于PONB的聚合物是一种可行的替代PEG生物结合的替代品.
- 这些聚合物保持生物活性,同时改善免疫识别配置文件.
- 在治疗性蛋白质中,PONB-Zwit为降低免疫性提供了一个有前途的选择.
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