Proline‐containing peptides—New insight and implications: A Review

The family of regulatory proline-containing peptides (PCPs), also known as glyprolines, exhibit significant biological activity. The group of glyprolines includes Gly-Pro (GP), Pro-Gly-Pro (PGP), cyclic Gly-Pro (cGP), as well as PGP derivatives, for example, N-acetylated PGP (N-a-PGP) and N-methylated PGP (N-m-PGP). PCPs are engaged in various biological processes including the proinflammatory neutrophil chemoattraction in lung diseases, inflammatory bowel diseases or ischemic stroke. Glyprolines have been also postulated to play an important role as atheroprotective and anticoagulant agents, exhibit neuroprotective effects in Parkinson's disease, as well as regulate insulin-like growth factor (IGF) homeostasis. It was also noticed that PCPs inhibit proliferation and migration of keratinocytes in wound healing, protection of the gastric mucosa and stimulation of its regeneration. The regulatory glyprolines are derived from endogenous and exogenous sources. Most PCPs are derived from collagen or diet protein degradation. Recently, great interest is concentrated on short proline-rich oligopeptides derived from IGF-1 degradation. The mechanism of PCPs biological activity is not fully explained. It involves receptor-mediated mechanisms, for example, N-a-PGP acts as CXCR1/2 receptor ligand, whereas cGP regulates IGF-1 bioavailability by modifying the IGF-1 binding to the IGF-1 binding protein-3. PGP has been observed to interact with collagen-specific receptors. The data suggest a promising role of PGP as a target of various diseases therapy. This review is focused on the effect of PCPs on metabolic processes in different tissues and the molecular mechanism of their action as an approach to pharmacotherapy of PCPs-dependent diseases.