2,5-diketopiperazines (DKP) are the simplest cyclo-peptides in nature and probably could play a key role in the origin (chemical evolution) of life [1]. They are ubiquitous in the environment: either in microorganisms (bacteria, fungi) or higher species (algae, lichens, marine sponges, gorgonians, tunicates, plants, animals venom), but also in food and beverages [2]. These natural dipeptides have been known since the beginning of the 20th century [3] but they have been neglected for a long time. Only recently, DKPs, especially proline-containing cyclo-dipeptides, have been enjoyed greater and greater significant interest due to their unique rigid heterocyclic structure, with diverse substituted functional groups, and a wide range of bioactivities, such as anticancer, antiviral, neuroprotective in neurodegenerative diseases, cytotoxic, antioxidant, antibacterial, antifungal, antimutagenic, anti-inflammatory or antihyperglycemic. They have relevance in ion-transport, quorum sensing, cell-cell signaling, as a system of the brain delivery of drugs with low permeability to cross the blood-brain barrier [4] and have a high affinity to a large number of receptors [2]. Short cyclic peptides have numerous favorable features, such as inter alia low toxicity, increased cell permeability, good bioavailability, binding affinity, or target selectivity [5]. Proline-containing peptides are more resistant to degradation by enzymes.
This presentation is focused on the survey of the high potential of proline-containing DKPs in medicinal use in the nearest future, in light of the newest scientific literature.
References
1. Ying J.; Lin, R.; Xu, P.; Wu, Y.; Zhao, Y. Scientific Reports. 2018, 8, 936.
2. Borthwick, A.D. Chem. Rev. 2012, 112, 3641.
3. Corey, R. J.Am.Chem.Soc. 1938, 60(7), 1598.
4. Cornacchia, C.; Cacciatore, I.; Baldassarre, L.; Mollica, A.; Feliciani, F.; Pinnen, F. Mini Reviews in Medicinal Chemistry. 2012.
5. Feni, L.; Jutten, L.; Parente, S.; Piarulli, U.; Neundorf, I.; Dia, D. Chem. Commun. 2020, 56, 5685.
