title: Linear and Cyclic Depsipeptidomimetics with β-Lactam Cores: A Class of New αvβ3Integrin Receptor Inhibitors.
abstract: The αvβ3integrin receptor plays an important role in tumor metastasis and tumor-induced angiogenesis. The inhibition of this receptor with diverse ligands, antibodies, or cyclic peptides is a promising research field for the treatment of a variety of tumors. The replacement of Phe-(Me)Val dipeptide by a β-lactam ring in Cilengitide has led to new products that show higher inhibitory activity than the parent cyclopeptide. In particular, substitution of a peptide bond β-lactam-NH-Asp linkage by a β-lactam-O-Asp ester linkage increases the activity of the new cyclodepsipeptide. In the same way it has been found that open-chain compounds of the form Asp-β-lactam-Arg can interact with the receptor and inhibit its activity moderately. The integrin inhibitory activity of the synthesized compounds has been established by using the CGH array, a method that appears to be a more reliable trial than the classical adhesion test.
authors.affiliation: Departamento de Química Orgánica-I, Facultad de Química, Universidad del País Vasco UPV/EHU, Paseo Manuel Lardizabal-3, 20018, San Sebastian, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Zabala-Uncilla
authors.affiliation: SGIKer NMR Facility, Universidad del País Vasco UPV/EHU, Joxe Mari Korta R&D Center, Avenida Tolosa-72, 20018, San Sebastian, Spain.
authors.forename: José I
authors.initials: JI
authors.lastname: Miranda
authors.affiliation: Genetadi Biotech A. G., Edificio 502, Parque Tecnológico de Bizkaia, 48160, Derio, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laso
authors.affiliation: Genetadi Biotech A. G., Edificio 502, Parque Tecnológico de Bizkaia, 48160, Derio, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fernández
authors.affiliation: Departamento de Química Orgánica-I, Facultad de Química, Universidad del País Vasco UPV/EHU, Paseo Manuel Lardizabal-3, 20018, San Sebastian, Spain.
authors.forename: Jose I
authors.initials: JI
authors.lastname: Ganboa
authors.affiliation: Departamento de Química Orgánica-I, Facultad de Química, Universidad del País Vasco UPV/EHU, Paseo Manuel Lardizabal-3, 20018, San Sebastian, Spain.
authors.forename: Claudio
authors.initials: C
authors.lastname: Palomo
mesh_terms: D047630:Depsipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000494:pharmacology*; D012910:Snake Venoms / Q000737:chemistry / Q000494:pharmacology; D047090:beta-Lactams / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D047630:Depsipeptides; D039302:Integrin alphaVbeta3; D057786:Peptidomimetics; D012910:Snake Venoms; D047090:beta-Lactams; C000622614:cyclo-((3-oxy-4-(1,2-dihydroxyethyl)-1-methylcarbonylazetidin-2-one)-Arg-Gly-Asp); C422910:Cilengitide
keywords: angiogenesis; cyclodepsipeptidomimetics; inhibitors; integrins; peptidomimetics