Thermodynamic and Structural Impact of α,α-Dialkylated Residue Incorporation in a β-Hairpin Peptide.

Peptides containing α,α-dialkylated α-amino acids, owing to their ability to disrupt aggregation of β-amyloid proteins, have therapeutic potential in the treatment of neurodegenerative diseases. Thermodynamic and structural analyses are reported for a series of β-hairpin peptides containing α,α-dialkylated α-amino acids with varying side-chain lengths. The results of these experiments show that α,α-dialkylated α-amino acids with side-chain lengths longer than one carbon unit are tolerated in a β-hairpin, although at a moderate cost to folded stability.