Proline-glycine-proline and N-acetyl-proline-glycine-proline (PGP and Ac-PGP)

Proline-glycine-proline (PGP) and N-acetyl-proline-glycine-proline (Ac-PGP) are collagen-derived tripeptides that function as potent neutrophil chemoattractants and matrikines. They are generated from the breakdown of extracellular matrix collagen by the sequential action of matrix metalloproteinases, such as MMP-8 and MMP-9, and prolyl endopeptidase (PE) (Gaggar et al., 2008; PubMed). These peptides possess a structural motif that mimics the ELR (Glu-Leu-Arg) motif found in CXC chemokines, allowing them to bind and activate the G protein-coupled receptors CXCR1 and CXCR2. In chronic inflammatory conditions, particularly in the lungs, an imbalance between the production and degradation of PGP/Ac-PGP leads to persistent neutrophil infiltration and tissue damage. The primary enzyme responsible for the degradation of PGP is leukotriene A4 hydrolase (LTA4H), which possesses an aminopeptidase activity distinct from its epoxide hydrolase activity (Snelgrove et al., 2010; Science). Elevated levels of Ac-PGP are found in the sputum of patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis, where they serve as biomarkers of disease severity. Therapeutic strategies focus on neutralizing these peptides using agents like the RTR peptide or modulating the enzymes responsible for their synthesis and degradation.

Other names

PGPAc-PGPN-acetyl-PGPN-Ac-PGPCollagen-derived matrikinePro-Gly-Pro

PGP and Ac-PGP act as agonists for the CXCR1 and CXCR2 receptors, mimicking the ELR (Glu-Leu-Arg) motif of CXC chemokines to induce neutrophil chemotaxis and activation (Weathington et al., 2006; PubMed).