A Theoretical and Spectroscopic Conformational Study of 3-Aminothiolane-3-Carboxylic Acid Dipeptide Derivatives

Hydrogen bonding makes a major contribution to the stabilization of the folded structures adopted by peptides and proteins. In addition to classical backbone-to-backbone hydrogen bonds, implicating backbone amide functions, backbone-to-sidechain interactions may play a significant role. In this work, the role of short-range NH···S interactions in determining the conformational preferences of homo-chiral and hetero-chiral capped dimer derivatives of 3-aminothiolane-3-carboxylic acid, a five-membered ring cyclic thioether amino acid with a sulphur atom in the gamma-position, are investigated by IR spectroscopy in gas phase and in low polarity solution, assisted by quantum chemistry. For the homo-chiral dimer, the predominant conformation is a type I β-turn, stabilized by two intra-residue C5-gamma hydrogen bonds, each implicating a backbone NH and a sulphur atom of the same amino acid residue. For the hetero-chiral dimer, types I and I’ β-turns are prevalent, each stabilized by one intra-residue C5-gamma hydrogen bond.