title: Stable Peptides Instead of Stapled Peptides: Highly Potent αvβ6-Selective Integrin Ligands.
abstract: The αvβ6 integrin binds the RGD-containing peptide of the foot and mouth disease virus with high selectivity. In this study, the long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub-nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins. Computational studies were performed to disclose the molecular bases underlying the high binding affinity and receptor subtype selectivity of this peptide. Finally, the utility of the ligand for use in biomedical studies was also demonstrated here.
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstrasse 4, 85747, Garching, Germany.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Maltsev
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstrasse 4, 85747, Garching, Germany.
authors.forename: Udaya Kiran
authors.initials: UK
authors.lastname: Marelli
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstrasse 4, 85747, Garching, Germany.
authors.forename: Tobias G
authors.initials: TG
authors.lastname: Kapp
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Di Leva
authors.affiliation: DiSTABiF, Secondo Università di Napoli, Via Vivaldi 43, 81100, Caserta, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Maro
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, München, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Nieberler
authors.affiliation: Klinische Forschergruppe der Frauenklinik, University Hospital rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, München, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Reuning
authors.affiliation: Department of Nuclear Medicine, University Hospital rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, München, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Dipartimento di Farmacia, Università di Napoli Federico II, Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.affiliation: Institute for Advanced Study and Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstrasse 4, 85747, Garching, Germany. kessler@tum.de.
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D016023:Integrins / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; D008024:Ligands; D010455:Peptides; C073878:integrin alphavbeta6
keywords: cyclic peptides; integrin inhibitors; molecular imaging; subtype selectivity; αvβ6 integrin