α-Alkylated α-amino acids reduce the aggregation of unfolded peptides

Abstract

Aberrant aggregation complicates the development of bioactive peptides. Here, we generate new α-ethylated variants of proteinogenic amino acids and demonstrate that they reduce peptide aggregation through a mechanism distinct from their α-methylated counterparts. Whereas α-methylated residues reduce aggregation by favoring helix formation, α-ethylated residues prevent aggregation without promoting secondary structure.