Bioactive cyclic dipeptides.

Cyclic dipeptides are among the simplest peptide derivatives commonly found in nature. Most cyclic dipeptides found to date appear to have emerged as by-products of fermentation and food processing. However, many are endogenous to members of animal and plant kingdoms; these include cyclo(Pro-Leu), cyclo(Pro-Val), cyclo(Pro-Phe), cyclo(Ala-Leu), cyclo(Pro-Tyr), cyclo(Pro-Trp), and cyclo(His-Pro). Although the five cyclic dipeptides--cyclo(His-Pro), cyclo(Leu-Gly), cyclo(Tyr-Arg), cyclo(Asp-Pro), and cyclo(Pro-Phe)--exhibit interesting physiological and/or pharmacological activities in mammals, only one of these, cyclo(His-Pro), has been conclusively shown to be endogenous to mammals. On the other hand, cyclo(Leu-Gly), cyclo(Tyr-Arg), and cyclo(Asp-Pro) are structurally related to endogenous peptides Pro-Leu-Gly-NH2 (melanocyte-stimulating hormone release inhibiting factor), Tyr-Arg (kyotorphin), and Val-Pro-Asp-Pro-Arg (enterostatin), respectively, which may serve as precursor peptides. It needs to be determined, however, whether these peptides can indeed result from the processing of their respective precursors. In conclusion, it appears that cyclic dipeptides are a relatively unexplored class of bioactive peptides that may hold great promise for the future.