Employing Broad Substrate Specificity of Omniligase to Generate Phage-Encoded Bicyclic Peptide Libraries for Ligand Discovery
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 <i>K</i><sub>D</sub> value of 1.5 μM, 100-fold lower than its linear version, demonstrating the utility of this platform for discovering bicyclic peptide ligands.
Authors
- Huimin Wei (ORCID: https://orcid.org/0000-0002-7989-3803)
- Xiao-Cui Wan
- Ge‐Min Fang (ORCID: https://orcid.org/0000-0003-4149-4062)
- Ying Chen (ORCID: https://orcid.org/0009-0005-8351-6620)
- Hua Zhang (ORCID: https://orcid.org/0000-0001-9518-740X)
- Wenjing Zhu (ORCID: https://orcid.org/0009-0008-4764-3261)
- Yanni Zhang (ORCID: https://orcid.org/0000-0003-2856-3182)
- Yuxuan Wang (ORCID: https://orcid.org/0009-0002-5716-6776)
- Feng-Hao Zheng
- Jun-Hao Xue
Institutions
- Anhui University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1021/acs.orglett.5c01205
- Citations
- 1
- Primary Topic
- Biochemical and Structural Characterization
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Natural Science Foundation of China