Structure-based approaches to inhibition of erbB receptors with peptide mimetics.
The epidermal growth factor (EGF) family of tyrosine kinase receptors (erbB receptors) are expressed at high levels in a wide variety of human cancers and have been associated with various features of advanced disease and poor prognosis. Therapeutic blockade of erbB signaling is a novel approach to the treatment of human tumors that could offer a noncytotoxic alternative to cancer treatment. A number of monoclonal antibodies (MAbs) directed against erbB receptors have been developed and demonstrated promising therapeutic results. We have designed small-molecule peptide mimetics of an anti-erbB rhu MAb 4D5 that can mimic structural and functional properties of the parental antibody. An alternative structure-based strategy of erbB receptor blockade with peptide mimetics by targeting receptor dimerization interfaces is also described.
Berezov
Alan
A
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, and the Abramson Family Cancer Research Institute, Philadelphia, PA 19104, USA.
Greene
Mark I
MI
Murali
Ramachandran
R
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D032701:Biomimetics; D019281:Dimerization; D010455:Peptides / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases