title: Synthetic ligands able to interact with the p53 tetramerization domain. Towards understanding a protein surface recognition event.
abstract: The applied interaction of synthetic molecules with defined regions of protein surfaces is an emerging strategy for the modulation of protein activity and/or stability. In spite of recent advances, the design of these molecules is not trivial. Among the most challenging aspects in designing these compounds is that they must compete with water molecules for interaction with polar patches of protein surfaces. Herein is reported the preparation of an arginine-rich peptide that interacts in aqueous solution with a very hydrophilic patch at the surface of the tetramerization domain of the tumor suppressor protein p53. The interaction has been studied by several complementary techniques. By using this peptide as a template, a library of peptides has been prepared and evaluated in order to examine the different factors that contribute to the recognition event. The conclusions extracted from this work could be useful for the design of ligands directed at highly hydrophilic protein surface patches.
authors.affiliation: Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Martinell
authors.forename: Xavier
authors.initials: X
authors.lastname: Salvatella
authors.forename: Jimena
authors.initials: J
authors.lastname: Fernández-Carneado
authors.forename: Susana
authors.initials: S
authors.lastname: Gordo
authors.forename: Miguel
authors.initials: M
authors.lastname: Feliz
authors.forename: Margarita
authors.initials: M
authors.lastname: Menéndez
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D001665:Binding Sites; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
chemical_list: D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D016159:Tumor Suppressor Protein p53