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

Abstract

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.

A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles

“…In kidney of streptotozin-induced diabetic mice and in diabetic patients, γ-Glu-ε-Lys seems to contribute to alterations in epithelial cell viability and tubular atrophy [ 35 ]. Alterations in dipeptide concentrations have been described for cancer [ 36 ], Parkinson disease [ 1 ], Alzheimer [ 37 ], Huntington disease [ 38 ], bronchopulmonary disease [ 39 ] or diabetes [ 35 , 40 ] and further studies in respective disease states are of interest.…”

“…For example, treatment with carnosine or anserine prevented alterations of renal function in diabetic (db/db) mice [29][30][31]. Additionally, for proline-containing dipeptides the biological activities seem to be not only based on the free amino acid alone [1]; for Tyr-containing dipeptides [32] an inhibitory effect on ACE activity has been demonstrated, and Tyr-Asp improves plant tolerance to oxidative stress by directly interfering with glucose metabolism [33]. Gly-containing dipeptides can provide osmoregulation in preimplantation embryos [34].…”

“…Blood and tissue dipeptides may originate from dietary intake and endogenous metabolism, i.e., protein degradation and synthesis [ 1 ]. Intestinal dipeptide uptake is mediated by peptide transporters (such as SLC15A1/PepT1 and SLCA2/PepT2 [ 2 , 3 ]).…”

Pharmacotranscriptomics of peptide drugs with neuroprotective properties

“…New peptide preparations belonging to the class of glyprolins are becoming increasingly important. They contain GP, have increased metabolic stability, are involved in various biological processes, including the proinflammatory chemoattraction of neutrophils in lung diseases, inflammatory bowel diseases or in ischemic stroke 62 . One of the simplest glyprolins is the PGP peptide and studies have shown that the PGP peptide has antiulcer and anti‐inflammatory effects 63,64 .…”

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts

“…EGFR is a member of the transmembrane receptor tyrosine kinases (ERBB family) which requires dimerization of receptor subunits for autophosphorylation inducing further signaling [21,22]. This process leads to the induction of proliferation, differentiation, and migration of the cells through the phosphorylation of proteins in several signaling pathways [23][24][25]. The key EGFR downstream signaling involves the PI3K/AKT/mTOR, Ras/Raf/ERK, and JAK/STAT pathways [6,26,27].…”