Phage Display of Graspeptides via SrtA-Mediated Peptide Ligation and Cyclization
We report a chemoenzymatic strategy for generating graspeptide mimetics. This strategy exploits the compatibility of sortase with the ester group at the X position of the pentapeptide sequence (LPXTG). Six types of graspeptide mimetics, including monocyclic and bicyclic depsipeptides, were generated. Combined with phage display, we identified a bicyclic depsipeptide targeting TEAD4 with a K<sub>D</sub> value of 2.2 μM. This study demonstrates the potential of peptiligase-based system for constructing cyclic peptide libraries with unique topologies.
Authors
- Zhixiu Xia (ORCID: https://orcid.org/0000-0001-6921-7257)
- Huimin Wei (ORCID: https://orcid.org/0000-0002-7989-3803)
- Fan Wu (ORCID: https://orcid.org/0000-0001-7900-7536)
- Xiao-Cui Wan
- Ge‐Min Fang (ORCID: https://orcid.org/0000-0003-4149-4062)
- Yanni Zhang (ORCID: https://orcid.org/0000-0003-2856-3182)
- Yu‐Xuan Wang (ORCID: https://orcid.org/0000-0002-6502-2636)
- Yue Hou (ORCID: https://orcid.org/0009-0005-4383-4384)
- Jun-Hao Xue
Institutions
- Anhui University (CN)
- Anhui Medical University (CN)
- Chinese Academy of Sciences (CN)
- Hefei Institutes of Physical Science (CN)
- High Magnetic Field Laboratory (CN)
- Life Care Institute of Medical Sciences & Research (IN)
- Huainan Normal University (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-11-04
- DOI
- https://doi.org/10.1021/acs.orglett.5c03982
- Primary Topic
- Biochemical and Structural Characterization
- Type
- article
- Field-Weighted Citation Impact
- 0.00