Synthesis of peptides containing oxo amino acids and their crystallographic analysis.

Abstract

An isolated uncharged hydrogen bond acceptor such as the carbonyl functionality of an aldehyde or a keto group is absent in natural amino acids. Although glutamine and asparagine are known to hydrogen bond through the amide carbonyl group in their side chains, they also possess the amide NH2 group, which can act as a hydrogen bond donor. This makes the structural study of peptides containing an oxo residue, with an isolated carbonyl group in the side chain, interesting. Here, we report the synthesis of δ- and ε-oxo amino acids and their incorporation into oligopeptides as the N-terminal residue. The resultant oxo peptides were extensively studied using X-ray crystallography to understand the interactions offered by the oxo group in peptide crystals. We find that the oxo groups are capable of providing additional hydrogen bonding opportunities to the peptides, resulting in increased intermolecular interactions in crystals. The study thus offers avenues for the utilization of oxo residues to introduce intermolecular interactions in synthetic peptides.