Construction of Nonnatural Cysteine-Cross-Linked Phage Libraries.

Phage display is a powerful technique for rapid construction and screening of peptide libraries with over 10 ⁹ sequence diversity. The M13 bacteriophage genome can be edited to incorporate randomized amino acids, which will be displayed on its minor coat protein (pIII). To enable screening of nonnatural cyclic peptides on phage, the minor coat protein can be modified with a chemical cross-linker. By taking advantage of the nucleophilicity and low abundance of free cysteines on phage, a variety of cysteine cross-linkers can be installed on the pIII protein. Here, we describe the construction of a chemically modified cyclic phage library through a cysteine cross-linking reagent, 1,3-dichloroacetone (DCA).
(© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)