Proline-glycine-proline peptide (PGP)

Proline-glycine-proline (PGP) is a tripeptide matrikine, a bioactive fragment derived from the proteolytic degradation of extracellular matrix collagen [2, 7]. It is produced through a sequential cascade involving matrix metalloproteinases (MMP-8 and MMP-9) and prolyl endopeptidase (PREP), which cleave native collagen into smaller peptide fragments [4, 16]. PGP exists in both an unmodified state and a more potent, stable N-acetylated form (Ac-PGP), both of which act as powerful chemoattractants for neutrophils by mimicking the ELR+ motif of chemokines like interleukin-8 (IL-8) and signaling through the CXCR1 and CXCR2 receptors [4, 5, 13]. \n\nThis peptide is primarily implicated in the pathogenesis of chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis, where its persistence drives continuous neutrophilic inflammation, emphysema, and tissue remodeling [1, 2, 6]. Elevated levels of PGP in the airways correlate with clinical severity and the frequency of exacerbations, establishing it as both a significant biomarker and a viable therapeutic target [8, 11]. Drug development strategies focus on neutralizing the peptide directly with agents like the RTR peptide, inhibiting the biosynthetic enzymes PREP and MMPs, or enhancing its natural degradation via the aminopeptidase activity of leukotriene A4 hydrolase (LTA4H) [11, 16, 18].

Other names

N-acetyl-proline-glycine-prolineAc-PGPN-alpha-acetyl-PGPPro-Gly-ProCollagen-derived matrikinePGP peptide

Proline-glycine-proline peptide acts as a chemoattractant for neutrophils by mimicking the structural motif of ELR+ chemokines and activating the G protein-coupled receptors CXCR1 and CXCR2 [4, 13]. Therapeutic modulation of this target involves direct peptide neutralization (e.g., using the RTR peptide), inhibition of the proteolytic enzymes (MMP-8, MMP-9, and prolyl endopeptidase) responsible for its generation from collagen, or facilitating its enzymatic degradation by leukotriene A4 hydrolase (LTA4H) [11, 16, 18].