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Identification of a cyclic peptide inhibitor of platelet‐derived growth factor–BB receptor‐binding and mitogen‐induced DNA synthesis in human fibroblasts
Author(s) -
Brennand David M.,
Dennehy Ulla,
Ellis Vincent,
Scully Michael F.,
Tripathi Poonam,
Kakkar Vijay V.,
Patel Geeta
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00885-5
Subject(s) - platelet derived growth factor receptor , platelet derived growth factor , receptor , peptide , growth factor , dna synthesis , cyclic peptide , microbiology and biotechnology , biology , biochemistry , chemistry , dna
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 125 I‐labelled PDGF‐BB but not for 125 I‐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.