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-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.
Brennand
D M
DM
Leopold Muller Laboratory, Thrombosis Research Institute, Chelsea, London, UK. brennand@tri-london.ac.uk
Dennehy
U
U
Ellis
V
V
Scully
M F
MF
Tripathi
P
P
Kakkar
V V
VV
Patel
G
G
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*
D019384:Nucleic Acid Synthesis Inhibitors; D010456:Peptides, Cyclic; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor