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

abstract

  • 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.

altmetric score

  • 6.2

author list (cited authors)

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

citation count

  • 12

publication date

  • September 2019

publisher