Abstract: The present disclosure relates to the design and generation of stapled helical peptides that perturb protein-protein interactions (PPIs). The methods disclosed herein for preparing stapled peptides involve providing a peptide having a first amino acid that is functionalized with a salicylaldehyde ester side group and a second amino acid functionalized with a 1,2-hydroxyl amine side group; reacting the first and second amino acids to generate an N,O-benzylidene acetal moiety; and performing acidolysis of the resultant N,O-benzylidene acetal moiety to generate the stapled peptide. In many forms, the stapled helical peptides described herein are not hydrophobic.

Abstract: The present disclosure relates to the design and generation of stapled helical peptides that perturb protein-protein interactions (PPIs). The methods disclosed herein for preparing stapled peptides involve providing a peptide having a first amino acid that is functionalized with a salicylaldehyde ester side group and a second amino acid functionalized with a 1,2-hydroxyl amine side group; reacting the first and second amino acids to generate an N,O-benzylidene acetal moiety; and performing acidolysis of the resultant N,O-benzylidene acetal moiety to generate the stapled peptide. In many forms, the stapled helical peptides described herein are not hydrophobic.