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

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A multi-domain peptide, PAB2-1c, was designed and synthesized as a bioactive mimic of PDGF. PBA2-1c bound to both α- and β-PDGF receptors as determined by surface plasmon resonance (SPR). The equilibrium dissociation constant (Kd) of binding to α-PDGF receptors by PAB2-1c (1.7 × 10− 8 M) compared favorably rhPDGF-AA (1.34 × 10− 8 M). Binding to β-PDGF receptor by PAB2-1c (2.2 × 10− 8 M) was less favorable than, that of recombinant human PDGFBB (1.59 × 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 μg/ml or lesser. The results support the hypothesis that, PBA2-1c is a mimetic of PDGF, although it has a more promiscuous receptor interaction.