Protein Chemical Synthesis Combined with Mirror-Image Phage Display Yields D-Peptide EGF Ligands that Block the EGF-EGFR Interaction
42 Pages Posted: 16 Apr 2019 Publication Status: Review Complete
More...Abstract
EGFR, the receptor for epidermal growth factor (EGF), is arguably considered the most important therapeutic target in contemporary anticancer treatments. However, 20 years after the introduction of anti-EGFR drugs into the clinical setting, a number of severe drawbacks have been observed, namely low tumour penetration of monoclonal antibodies, acquisition of resistance to tyrosine-kinase inhibitors, and complete lack of efficacy in several types of cancer. Here, we report the design of a strategy to obtain all-D peptides directed to EGF instead of EGFR and we demonstrate their ability to block efficiently the EGF-EGFR interaction. We report an efficient chemical synthesis of the enantiomeric version of human EGF. Combined with the use of mirror-image phage display, this strategy has allowed us to discovery several protease-resistant peptides able to bind to EGF. Using alpha-screen technology we have demonstrated the capacity of the best peptide candidates to disrupt the EGF-EGFR interaction.
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