Nonproteinogenic deep mutational scanning of linear and cyclic peptides.

ABSTRACT: High-resolution structure-activity analysis of polypeptides requires amino acid structures that are not present in the universal genetic code. Examination of peptide and protein interactions with this resolution has been limited by the need to individually synthesize and test peptides containing nonproteinogenic amino acids. We describe a method to scan entire peptide sequences with multiple nonproteinogenic amino acids and, in parallel, determine the thermodynamics of binding to a partner protein. By coupling genetic code reprogramming to deep mutational scanning, any number of amino acids can be exhaustively substituted into peptides, and single experiments can return all free energy changes of binding. We validate this approach by scanning two model protein-binding peptides with 21 dive

SUBMITTER: Rogers JM 

PROVIDER: S-EPMC6205457 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature