美国波士顿学院Jianmin Gao团队报道了一种具有长停留时间的赖氨酸靶向可逆共价抑制剂。相关研究成果于2022年1月18日发表在国际知名学术期刊《美国化学会杂志》。

研究人员报道了一种新的可逆赖氨酸结合物，与先前已知的亚氨基硼酸酯化学相比，该结合物具有一种新的二氮杂硼酸盐产物和慢得多的解离动力学。将二氮杂硼烷形成弹头RMR1与肽配体结合，可提供有效且长效的葡萄球菌分拣酶可逆共价抑制剂。

通过生物化学和基于细胞的试验证明了抑制sortase的有效性。RMR1和亚氨基硼酸形成弹头的比较研究强调了调节键解离动力学在获得长效可逆共价抑制剂方面的重要性和潜力。

附：英文原文

Title: Lysine-Targeting Reversible Covalent Inhibitors with Long Residence Time

Author: Rahi M. Reja, Wenjian Wang, Yuhan Lyu, Fredrik Haeffner, Jianmin Gao

Issue&Volume: January 18, 2022

Abstract: We report a new reversible lysine conjugation that features a novel diazaborine product and much slowed dissociation kinetics in comparison to the previously known iminoboronate chemistry. Incorporating the diazaborine-forming warhead RMR1 to a peptide ligand gives potent and long-acting reversible covalent inhibitors of the staphylococcal sortase. The efficacy of sortase inhibition is demonstrated via biochemical and cell-based assays. A comparative study of RMR1 and an iminoboronate-forming warhead highlights the significance and potential of modulating bond dissociation kinetics in achieving long-acting reversible covalent inhibitors.

DOI: 10.1021/jacs.1c12702

Source: https://pubs.acs.org/doi/10.1021/jacs.1c12702