title: Identification of a cyclic peptide inhibitor of platelet-derived growth factor-BB receptor-binding and mitogen-induced DNA synthesis in human fibroblasts.
abstract: Peptides corresponding to residues from Loops I and III of platelet-derived growth factor-BB (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-BB(73-81), on DNA synthesis was shown to be restricted to cells which express PDGF receptors. Also cyclic PDGF-BB(73-81) specifically competed for 125I-labelled PDGF-BB but not for 125I-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-BB(73-81) in the native molecule. The cyclic peptide may constitute a basis for developing more potent inhibitors of PDGF action.
authors.affiliation: Leopold Muller Laboratory, Thrombosis Research Institute, Chelsea, London, UK. brennand@tri-london.ac.uk
authors.forename: D M
authors.initials: DM
authors.lastname: Brennand
authors.forename: U
authors.initials: U
authors.lastname: Dennehy
authors.forename: V
authors.initials: V
authors.lastname: Ellis
authors.forename: M F
authors.initials: MF
authors.lastname: Scully
authors.forename: P
authors.initials: P
authors.lastname: Tripathi
authors.forename: V V
authors.initials: VV
authors.lastname: Kakkar
authors.forename: G
authors.initials: G
authors.lastname: Patel
mesh_terms: D000595:Amino Acid Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D010456:Peptides, Cyclic; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor