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

Proline-glycine-proline (PGP) and its acetylated form, N-acetyl-PGP (Ac-PGP), are collagen-derived tripeptides that function as potent neutrophil chemoattractants and are classified as matrikines. They are generated through a sequential proteolytic cascade where extracellular matrix collagen is cleaved by matrix metalloproteinases, specifically MMP-8 and MMP-9, followed by further processing by the enzyme prolyl endopeptidase (PE) (Gaggar et al., 2011; Weathington et al., 2006). These peptides act as molecular mimics of the chemokine Interleukin-8 (CXCL8), binding to and activating the CXCR1 and CXCR2 receptors on neutrophils to drive persistent pulmonary inflammation (Weathington et al., 2006). Under normal physiological conditions, PGP is degraded by the aminopeptidase activity of leukotriene A4 hydrolase (LTA4H); however, in chronic inflammatory diseases like COPD and cystic fibrosis, this degradation is often impaired by cigarette smoke or oxidative stress, leading to a self-sustaining cycle of neutrophil recruitment and tissue damage (Snelgrove et al., 2010). Therapeutic interventions currently under investigation include the use of neutralizing antibodies against PGP, the administration of exogenous LTA4H, or the use of small molecule inhibitors to block the enzymes responsible for PGP synthesis (O'Reilly et al., 2009).

Other names

N-acetyl-PGPAc-PGPPGPCollagen-derived matrikineN-alpha-acetyl-Pro-Gly-ProN-Ac-PGP

Neutralization of the tripeptide to prevent binding to CXCR1 and CXCR2 receptors, or inhibition of enzymes such as Matrix Metalloproteinases (MMP-8, MMP-9) and Prolyl Endopeptidase (PE) involved in its generation from collagen.