小柯机器人

Azaphilones as Activation-Free Primary-Amine-Specific Bioconjugation Reagents for Peptides, Proteins and Lipids
2021-11-30 15:32

南京大学姚祝军团队开发出为多肽、蛋白质和脂类进行特异性生物偶联的新方法。2021年11月26日,《德国应用化学》杂志在线发表了这项成果。

受天然vinylogous γ-pyridone(vPDN)生成机制的启发,研究人员开发了一种新颖独特的、基于azaphilone的、无活化的初级胺选择性生物偶联方法。这个策略通过生成高度稳定的vPDN连接,使肽和蛋白质(包括临床使用的治疗性抗体曲妥珠单抗)中的伯胺基团方便地功能化。对伯胺的出色化学选择性也使azaphilone衍生物能够特异性地修饰革兰氏阳性细菌的脂质成分,而避开革兰氏阴性细菌和哺乳动物细胞。
 
这种新方法显示出明显的优势,包括化学选择性、效率、灵活性和生物相容性,因此为目前的生物分子偶联工具箱提供了宝贵的补充。
 
据悉,生物大分子的残基选择性生物结合方法受到高度关注,可用于扩大其生物和医学应用范围。
 
附:英文原文

Title: Azaphilones as Activation-Free Primary-Amine-Specific Bioconjugation Reagents for Peptides, Proteins and Lipids

Author: Shandong Yi, Siyuan Wei, Qingsong Wu, Huan Wang, Zhu-Jun Yao

Issue&Volume: 2021-11-26

Abstract: Residue-selective bioconjugation methods for biomolecules are highly sought to expand the scope of their biological and medical applications. Inspired by the generation mechanism of natural vinylogous  γ  -pyridones (vPDNs), we have developed a novel unique azaphilone-based, activation-free primary amine-selective bioconjugation method for biomolecules. Our strategy allows facile functionalization of primary amine groups in peptides and proteins, including the clinically used therapeutic antibody trastuzumab, by generating a highly stable vPDN linkage. Excellent chemoselectivity toward primary amines also enables the azaphilone derivatives to specifically modify the lipid components of Gram-positive bacteria while bypassing Gram-negative bacteria and mammalian cells. The new method shows significant advantages including chemoselectivity, efficiency, flexibility and biocompatibility, and therefore provides a valuable addition to the current toolbox for biomolecule conjugation.

DOI: 10.1002/anie.202111783

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202111783

分享到:

0