A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library. Academic Article uri icon


  • Superior to linear peptides in biological activities, cyclic peptides are considered to have great potential as therapeutic agents. To identify cyclic-peptide ligands for therapeutic targets, phage-displayed peptide libraries in which cyclization is achieved by the covalent conjugation of cysteines have been widely used. To resolve drawbacks related to cysteine conjugation, we have invented a phage-display technique in which its displayed peptides are cyclized through a proximity-driven Michael addition reaction between a cysteine and an amber-codon-encoded N -acryloyl-lysine (AcrK). Using a randomized 6-mer library in which peptides were cyclized at two ends through a cysteine-AcrK linker, we demonstrated the successful selection of potent ligands for TEV protease and HDAC8. All selected cyclic peptide ligands showed 4- to 6-fold stronger affinity to their protein targets than their linear counterparts. We believe this approach will find broad applications in drug discovery.

published proceedings

  • Angew Chem Int Ed Engl

altmetric score

  • 6.2

author list (cited authors)

  • Wang, X. S., Chen, P., Hampton, J. T., Tharp, J. M., Reed, C. A., Das, S. K., ... Liu, W. R.

citation count

  • 40

complete list of authors

  • Wang, Xiaoshan Shayna||Chen, Peng-Hsun Chase||Hampton, J Trae||Tharp, Jeffery M||Reed, Catrina A||Das, Sukant K||Wang, Duen-Shian||Hayatshahi, Hamed S||Shen, Yang||Liu, Jin||Liu, Wenshe Ray

publication date

  • October 2019