A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library

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

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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 Nϵ-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.

Original languageEnglish
Pages (from-to)15904-15909
Number of pages6
JournalAngewandte Chemie - International Edition
Issue number44
StatePublished - 28 Oct 2019


  • HDAC8
  • N-acryloyl-lysine
  • cyclic peptides
  • phage display
  • proximity-driven cyclization


Dive into the research topics of 'A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library'. Together they form a unique fingerprint.

Cite this