Peptide and peptide library cyclization via bromomethylbenzene derivatives.

Cyclization confers several advantages to peptides, cumulatively serving to make them more drug-like. In this protocol, cyclic peptides are generated via bis-alkylation of cysteine-containing peptides using α,α'-dibromo-m-xylene. The reactions are robust and high yielding. Multiple reaction platforms for the application of this versatile strategy are described herein: the cyclization of solid-phase-synthesized peptides, both in solution and on resin, as well as the cyclization of in vitro translated mRNA-peptide fusion libraries on oligo(dT) resin.