Wan Xiao-Cui, Zhu Wen-Jing, Wei Hui-Min, Zhang Yan-Ni, Zheng Feng-Hao, Zhang Hua, Chen Ying, Xue Jun-Hao, Wang Yu-Xuan, Fang Ge-Min
Institute of Health Sciences and Technology, Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, People's Republic of China.
Org Lett. 2025 May 2;27(17):4592-4596. doi: 10.1021/acs.orglett.5c01205. Epub 2025 Apr 17.
We report an enzymatic cyclization strategy termed omniligase-mediated peptide bicyclization. An electrophilic group was introduced into the recognition sequence of omniligase to achieve intramolecular bicyclization with Cys residues. In combination with phage display, we identified a bicyclic peptide ligand targeting TEAD4 with a value of 1.5 μM, 100-fold lower than its linear version, demonstrating the utility of this platform for discovering bicyclic peptide ligands.
我们报道了一种称为全连接酶介导的肽双环化的酶促环化策略。将一个亲电基团引入全连接酶的识别序列中，以实现与半胱氨酸残基的分子内双环化。结合噬菌体展示技术，我们鉴定出一种靶向TEAD4的双环肽配体，其解离常数为1.5 μM，比其线性形式低100倍，证明了该平台在发现双环肽配体方面的实用性。
