A synthetic, bioactive PDGF mimetic with binding to both α-PDGF and β-PDGF receptors

A multi-domain peptide, PAB2-1c, was designed and synthesized as a bioactive mimic of PDGF. PBA2-1c bound to both alpha- and beta-PDGF receptors as determined by surface plasmon resonance (SPR). The equilibrium dissociation constant (Kd) of binding to alpha-PDGF receptors by PAB2-1c (1.7 x 10(-8) M) compared favorably rhPDGF-AA (1.34 x 10(-8) M). Binding to -PDGF receptor by PAB2-1c (2.2 x 10(-8) M) was less favorable than, that of recombinant human PDGFBB (1.59 x 10(-9) M). Interestingly, PBA2-1c bound to these two receptors with similar affinity suggesting that, PBA2-1c was not PDGF receptor selective. In a murine myoblast cell line C2C12, PBA2-1c increased the tyrosine phosphorylation on PDGF receptors and the phosphorylation of AKT and ERK1/2 in a concentration-related manner. PBA2-1c also stimulated an increase in cell proliferation, cell migration, and collagen gel contraction. In these cell-based assays, PAB2-1c was effective at 1 microg/ml or lesser. The results support the hypothesis that PBA2-1c is a mimetic of PDGF, although it has a more promiscuous receptor interaction.