Discovery of a 29-Amino-Acid Reactive Abiotic Peptide for Selective Cysteine Arylation.

ABSTRACT: The regio- and chemoselective modification of proteins or peptides with chemical reagents is often challenging. One approach to overcome this problem involves identifying abiotic polypeptide sequences that react with specific small molecules. Toward this goal, we profiled ∼5 × 10¹³ randomized 30-mer peptides using mRNA display and high-throughput sequencing in search of polypeptides that can undergo cysteine arylation with a water-soluble perfluoroarene. Within this vast chemical space, we discovered a cysteine-containing sequence with a second-order rate constant of 0.29 M^-1 s^-1 for arylation. An N- and C-terminal truncation reduced the reaction rate, as did the addition of denaturants. When the reactive peptide was covalently fused to the enzyme Sortase A

SUBMITTER: Evans ED 

PROVIDER: S-EPMC5856623 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature