Identification of a cyclic peptide inhibitor of platelet-derived growth factor-BB receptor-binding and mitogen-induced DNA synthesis in human fibroblasts

Peptides corresponding to residues from Loops I and III of platelet-derived growth factor-BE (PDGF-BB) were examined for their potential to act as PDGF antagonists, We have identified two peptides which directly stimulated DNA synthesis in human dermal fibroblasts and a cyclic peptide which inhibited PDGF-induced DNA synthesis. The inhibitory action of cyclic PDGF-BB73-81 on DNA synthesis was shown to be restricted to cells which express PDGF receptors. Also cyclic PDGF-BB73-81 specifically competed for I-125-labelled PDGF-BB but not for I-125-labelled EGF binding to their respective cellular receptors. The cyclic peptide therefore provides a minimum structure to investigate PDGF/receptor interactions and our findings confirm the importance of the loop configuration of PDGF-BB73-81 in the native molecule, The cyclic peptide may constitute a basis for developing more potent inhibitors of PDGF action. (C) 1997 Federation of European Biochemical Societies.