title: Rational design for the development of epidermal growth factor receptor antagonists.
abstract: Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) bind with similar high affinity to the human EGF receptor. Using a domain-exchange strategy we have shown that the C-terminal linear region of these molecules is involved in high affinity receptor binding. By further single amino acid substitution in this linear C-terminal region, a putative interaction site of these ligands with their receptor has been identified. This identification of a receptor binding domain in EGF/TGF alpha provides an important initial step in the development of EGF receptor antagonists with significant clinical potential.
authors.affiliation: Department of Cell Biology, University of Nijmegen, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: van Zoelen
authors.forename: A E
authors.initials: AE
authors.lastname: Lenferink
authors.forename: R H
authors.initials: RH
authors.lastname: Kramer
authors.forename: M L
authors.initials: ML
authors.lastname: van de Poll
mesh_terms: D000595:Amino Acid Sequence; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
chemical_list: D066246:ErbB Receptors