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Updated: May 11, 2025

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases
Published on: August 27, 2021
Employing Broad Substrate Specificity of Omniligase to Generate Phage-Encoded Bicyclic Peptide Libraries for Ligand
Xiao-Cui Wan1, Wen-Jing Zhu1, Hui-Min Wei1
1Institute of Health Sciences and Technology, Institutes of Physical Science and Information Technology, Anhui University, Hefei 230601, People's Republic of China.
Abstract:
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 KD value of 1.5 μM, 100-fold lower than its linear version, demonstrating the utility of this platform for discovering bicyclic peptide ligands.
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