Flat 1103, Block 9, Heng Fa Chuen, Hong Kong.
Immunobiology. 2019 Nov;224(6):827-833. doi: 10.1016/j.imbio.2019.08.003. Epub 2019 Aug 13.
Alex Law and Paul Levine recall their work to establish the covalent bond between C3 and target surfaces. It started with a naive experiment by analyzing the membrane polypeptides of sheep erythrocytes bound with I-labelled C3. They found complexes with molecular weight higher than the individual C3 polypeptides. These complexes survived all conditions designed to disrupt non-covalent interactions. They then showed that the bond was an ester, with an active acyl group on C3 which reacted with a hydroxyl group on the acceptor molecule. With the discovery of an internal thioester by Jim Prahl, Jamila Janatova, Brian Tack and their colleagues, it became clear that the reaction was by an acyl transfer from the thioester of C3 to the target hydroxyl group. Later on they showed that C4 also bound covalently to target molecules. By establishing a fluid phase system to study the kinetics of the binding reactions of C3 and C4, Alex was able to continue the work in the MRC Immunochemistry Unit in Oxford from 1981, to eventually determine the chemical mechanism of the binding reaction. In order to give some sense of reality, this article is written as a narrative from Alex, who did the experiments. Both Alex and Paul are retired. Pauls lives on Martha's Vineyard where he writes occasional articles on science for one of the Island's newspapers. Alex lives in Hong Kong and tries to make some sense of the local politics.
亚历克斯·罗和保罗·莱文回忆起他们建立 C3 与靶表面之间共价键的工作。这项工作始于对与 I 标记的 C3 结合的绵羊红细胞膜多肽进行分析的一个天真实验。他们发现了分子量高于单个 C3 多肽的复合物。这些复合物经受住了所有旨在破坏非共价相互作用的条件。然后他们表明，该键是酯键，C3 上具有活性酰基基团，该基团与受体分子上的羟基反应。随着吉姆·普拉尔、贾米拉·贾纳托娃、布莱恩·塔克及其同事发现内部硫酯，很明显，该反应是通过 C3 的硫酯从酰基转移到靶羟基基团。后来，他们表明 C4 也与靶分子共价结合。通过建立一个流体相系统来研究 C3 和 C4 结合反应的动力学，亚历克斯能够从 1981 年开始在牛津 MRC 免疫化学单位继续这项工作，最终确定了结合反应的化学机制。为了给人一种真实感，本文是由亚历克斯以叙事的形式撰写的，他进行了实验。亚历克斯和保罗都已退休。保罗住在玛莎葡萄园岛，偶尔为岛上的一家报纸撰写科学文章。亚历克斯住在香港，试图理解当地的政治。
