title: Peptides Targeting EGF Block the EGF-EGFR Interaction.
abstract: Epidermal growth factor receptor (EGFR) is a key target in chemotherapy. Some drugs acting on the receptor are currently in use; however, drug resistance, which causes tumour relapse, calls for the discovery of alternative inhibitors. Using docking and receptor hotspot mimicry, we have designed novel peptides directed at EGF, the main growth factor ligand of EGFR. An array of biophysical techniques was used to characterise the structure and interaction of these ligands with the target protein. Both design methods identified peptides able to bind EGF, and the capacity of these peptides to inhibit the interaction between EGF and EGFR was demonstrated in two in vitro systems. Based on targeting the smaller companion of a protein-protein interaction, the new approach described herein can be envisaged as a parallel drug design strategy, and our compounds represent the first in a new class of binders that could serve as complementary compounds in potential multidrug cancer therapy.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Guardiola
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Díaz-Lobo
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Seco
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain. laura.nevola@irbbarcelona.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Nevola
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain. ernest.giralt@irbbarcelona.org.|Department of Organic Chemistry, University of Barcelona, 08028, Barcelona, Spain. ernest.giralt@irbbarcelona.org.
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019151:Peptide Library; D010455:Peptides; D054852:Small Molecule Libraries; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: SAW; cancer therapy; membrane receptors; peptides; protein-protein interaction