School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Biomacromolecules. 2022 Jan 10;23(1):454-463. doi: 10.1021/acs.biomac.1c01435. Epub 2021 Dec 8.
β-Hydroxybutyrate (3HB) is a small molecule produced as a ketone body in mammalian animals. It has been found that 3HB provides not only energy for a body, it also participates in cell signal transduction events as a signal molecule. This study focuses on investigation of 3HB immunomodulatory mechanisms. Proteomic analysis indicates a new post-translational modification of β-hydroxybutyrylation (Kbhb) on antibodies. Because of the low level of Kbhb antibodies and the associated difficulty in purifying them, simulated Kbhb antibody was produced using chemical modification . The chemically modified Kbhb antibody was shown to improve the stability of antibodies to protease and heat treatments. Furthermore, Kbhb of antibodies stabilizes the antibodies in plasma. As a remarkable example, COVID-19 neutralizing antibody B38 produced by 293T cells was Kbhb modified and stabilized , providing a strategy for the possibility of extending the protection effects of COVID-19 antibodies.
β-羟基丁酸（3HB）是哺乳动物体内产生的一种小分子酮体。研究发现，3HB 不仅为身体提供能量，还作为信号分子参与细胞信号转导事件。本研究专注于 3HB 免疫调节机制的研究。蛋白质组学分析表明，抗体上存在一种新的翻译后修饰——β-羟丁酰化（Kbhb）。由于 Kbhb 抗体的含量低，以及相关的纯化困难，本研究使用化学修饰的方法来产生模拟的 Kbhb 抗体。化学修饰的 Kbhb 抗体显示出提高了对蛋白酶和热处理的稳定性。此外，抗体上的 Kbhb 稳定了其在血浆中的存在。作为一个显著的例子，由 293T 细胞产生的 COVID-19 中和抗体 B38 经过 Kbhb 修饰和稳定化处理，为延长 COVID-19 抗体的保护效果提供了一种可能性的策略。
