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Immunologic Research

, Volume 27, Issue 2–3, pp 303–308 | Cite as

Structure-based approaches to inhibition of erbB receptors with peptide mimetics

  • Alan Berezov
  • Mark I. Greene
  • Ramachandran Murali
Article

Abstract

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.

Key Words

Antibodies Inhibitors HER2 Disabling erbB receptor ensembles Structure-based design Peptidomimetics 

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Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphia
  2. 2.the Abramson Family Cancer Research InstitutePhiladelphia

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