A new strategy for the selection of stapled peptide inhibitors by mRNA display

Hydrocarbon stapled peptides are promising therapeutics for inhibition of intracellular protein-protein interactions. Here we develop a new high-throughput strategy for hydrocarbon stapled peptide discovery based on mRNA display of peptides containing α-methyl cysteine and cyclized with m -dibromoxylene. We focus on development of a peptide binder to the HPV16 E2 protein. α-methyl Cys incorporation plus cyclization allows for the creation of α-helical libraries by mRNA display.