Rational design for the development of epidermal growth factor receptor antagonists.
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.
van Zoelen
E J
EJ
Department of Cell Biology, University of Nijmegen, The Netherlands.
Lenferink
A E
AE
Kramer
R H
RH
van de Poll
M L
ML
D000595:Amino Acid Sequence; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D066246:ErbB Receptors