School of Life Science, Institutes of Physical Science and Information Technology, Institute of Health Sciences, Anhui University, Hefei 230601, P.R. China.
Org Lett. 2024 Apr 5;26(13):2601-2605. doi: 10.1021/acs.orglett.4c00602. Epub 2024 Mar 26.
We report here an enzymatic strategy for asparaginyl endopeptidase-mediated peptide cyclization. Incorporation of chloroacetyl groups into the recognition sequence of AEP1 enabled intramolecular cyclization with Cys residues. Combining this strategy and phage display, we identified nanomolar macrocyclic peptide ligands targeting TEAD4. One of the bicyclic peptides binds to TEAD4 with a value of 139 nM, 16 times lower than its linear analogue, demonstrating the utility of this platform in discovering high-affinity macrocyclic peptide ligands.
我们在此报告了一种天冬酰胺内肽酶介导的肽环化的酶促策略。将氯乙酰基引入 AEP1 的识别序列中，使 Cys 残基能够进行分子内环化。结合该策略和噬菌体展示，我们鉴定了针对 TEAD4 的纳摩尔级别的大环肽配体。其中一个双环肽与 TEAD4 的结合常数为 139 nM，比其线性类似物低 16 倍，证明了该平台在发现高亲和力的大环肽配体方面的实用性。
