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-de rived growth factor-BE (PDGF-BB) were examined for their potential to act as PDGF antagonists, We have identified two peptides which directl y stimulated DNA synthesis in human dermal fibroblasts and a cyclic pe ptide which inhibited PDGF-induced DNA synthesis. The inhibitory actio n of cyclic PDGF-BB73-81 on DNA synthesis was shown to be restricted t o cells which express PDGF receptors. Also cyclic PDGF-BB73-81 specifi cally competed for I-125-labelled PDGF-BB but not for I-125-labelled E GF binding to their respective cellular receptors. The cyclic peptide therefore provides a minimum structure to investigate PDGF/receptor in teractions and our findings confirm the importance of the loop configu ration of PDGF-BB73-81 in the native molecule, The cyclic peptide may constitute a basis for developing more potent inhibitors of PDGF actio n. (C) 1997 Federation of European Biochemical Societies.