Investigation of the formation mechanism of proline-containing cyclic dipeptide from the linear peptide

Cyclic dipeptides, 2,5-diketopiperazines (DKPs), are well-known bioactive and taste compounds in food. DKPs have also been reported in various foods and particularly, Pro-containing DKPs (cyclo(-X-Pro)) are more predominant in heated and fermented foods than other type of DKPs. However, the mechanism underlying the preferential formation of Pro-containing DKPs in food remains uncertain. Herein, we attempted to elucidate the effects of reaction conditions and the mechanism of DKPs formation. The reaction conditions (heating time, heating temperature, and pH) and amino acid sequence of the linear peptides were important for the DKPs formation from linear peptides. In addition, Pro-containing DKPs were significantly formed from linear peptides with the second amino acid from the N-terminus being Pro. Based on these results, the underlying mechanism of the enrichment of Pro-containing DKPs in foods was proposed.