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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 Sneak Peek Status: Review Complete

See all articles by Cristina Díaz-Perlas

Cristina Díaz-Perlas

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Monica Varese

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Salvador Guardiola

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Macarena Sánchez-Navarro

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Jesús García

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Meritxell Teixidó

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Ernest Giralt

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

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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.

Suggested Citation

Díaz-Perlas, Cristina and Varese, Monica and Guardiola, Salvador and Sánchez-Navarro, Macarena and García, Jesús and Teixidó, Meritxell and Giralt, Ernest, Protein Chemical Synthesis Combined with Mirror-Image Phage Display Yields D-Peptide EGF Ligands that Block the EGF-EGFR Interaction (April 16, 2019). Available at SSRN: https://ssrn.com/abstract=3372967 or http://dx.doi.org/10.2139/ssrn.3372967
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Cristina Díaz-Perlas

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Parc Científic de Barcelona
C/ Baldiri Reixac 10
Barcelona, 08028
Spain

Monica Varese

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Parc Científic de Barcelona
C/ Baldiri Reixac 10
Barcelona, 08028
Spain

Salvador Guardiola

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Parc Científic de Barcelona
C/ Baldiri Reixac 10
Barcelona, 08028
Spain

Macarena Sánchez-Navarro

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Parc Científic de Barcelona
C/ Baldiri Reixac 10
Barcelona, 08028
Spain

Jesús García

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona)

Baldiri​ ​Reixac​ ​10
Barcelona, 08028
Spain

Meritxell Teixidó

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona) ( email )

Parc Científic de Barcelona
C/ Baldiri Reixac 10
Barcelona, 08028
Spain

Ernest Giralt (Contact Author)

The Barcelona Institute of Science and Technology (BIST) - Institute for Research in Biomedicine (IRB Barcelona) ( email )

Parc Científic de Barcelona
C/ Baldiri Reixac 10
Barcelona, 08028
Spain

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