A specific binding site for a fragment of the B-loop of epidermal growth factor and related peptides

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2002, Vol.23 (1), p.97-102
• Main Authors: Gembitsky, Dmitry S, Bozsó, Zsolt, O’Flaharty, Martina, Ötvös, Ferenc, Murphy, Richard F, Lovas, Sándor
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; B-loop fragment; Binding Sites; Cell Line; Cell Membrane - metabolism; Cysteine - chemistry; Dose-Response Relationship, Drug; Epidermal growth factor; Epidermal Growth Factor - chemistry; ErbB Receptors - metabolism; Humans; Ligands; Molecular Sequence Data; Peptide Biosynthesis; Peptides - chemistry; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Specific binding; Transforming growth factor alpha; Tumor Cells, Cultured
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/S0196-9781(01)00584-8

Fragments of the B-loop of the epidermal growth factor family of peptides are reported to have mitogenic and angiogenic properties but appear to fail to compete with radioiodinated EGF in receptor binding. In this study, 11 analogs of a fragment of the B-loop of EGF-related peptides from several species were synthesized to study binding to A431 human epidermoid carcinoma using both 125I-EGF and [3′4′- 3H-Tyr 22,29, Abu 20,31]EGF(20–31)-NH 2. Specific binding sites were found for the human fragment and 8 analogs at a density five times higher than that of the EGF receptors. Analogs did not compete with 125I-EGF for binding to the EGF receptor. The novel binding site may mediate the biological effects of the fragments. The primary rather than secondary structure of the fragments appears to determine affinity.