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有机化合物作为蛋白质/-聚合物结合的高效和高度特异性的链接剂

Paul Wilson¹, Athina Anastasaki¹, Matthew R Owen¹

¹†Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom.

Journal of the American Chemical Society

|March 21, 2015

概括

一种新的三价试剂通过向二硫化键,使得快速和特定的聚合物结合成为可能. 这种方法提供了高效率和正角性,具有创造先进生物结合物的潜力.

科学领域:

生物结合化学生物结合化学
聚合物化学聚合物化学
药用化学医学化学

背景情况:

开发高效和特定的方法,将和蛋白与聚合物结合起来,对于治疗应用至关重要.
现有的二硫化物键向策略面临着特异性和效率方面的挑战,特别是在自由硫醇的存在下.

研究的目的:

开发一种新的,以为驱动的结合策略,使用三价来进行/蛋白质-聚合物结合.
与现有技术相比,评估这种新方法的效率,特异性和直角性.
为生物结合应用合成和评估功能聚合物.

主要方法:

使用三价酸 (As(III)) 衍生物通过二硫化键桥接与鱼酸 (sCT) 结合.
采用了顺序减少-结合协议,并使用RP-HPLC和MALDI-ToF-MS来表征结合物.
通过水性单电子转移活基聚合和后聚合修饰合成的功能聚合物.

主要成果:

实现了快速 (t <2分钟) 和高效率的sCT固体测量结合,与领先的方法相提并论.
在牛血清专蛋白上表现出对二硫化键的增强特异性,超过牛血清专蛋白上的自由氨酸残留物,表明潜在的正交性.
合成了可忽略的细胞毒性水友性功能聚合物,这些聚合物成功与sCT结合.

结论:

三价试剂提供了一种高效和特定的方法,用于二硫化物键介导的生物结合.
这种方法提供了潜在的直角性,区分不同类型的dithiols.
通过这种途径合成的功能聚合物适合生物结合,具有潜在的治疗益处.

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