title: Computational design of novel peptidomimetic inhibitors of cadherin homophilic interactions.
abstract: We report a first set of peptidomimetic ligands mimicking the adhesive interface identified by recent crystallographic structures of E- and N-cadherin. Compounds 2 and 3 inhibit adhesion of epithelial ovarian cancer (EOC) cells with improved efficacy compared to the ADH-1 peptide, a N-cadherin antagonist that is in early clinical trials in EOC patients.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, I-20133, Milan, Italy. monica.civera@unimi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Doro
authors.forename: Cinzia
authors.initials: C
authors.lastname: Colombo
authors.forename: Chiara
authors.initials: C
authors.lastname: Alberti
authors.forename: Daniela
authors.initials: D
authors.lastname: Arosio
authors.forename: Laura
authors.initials: L
authors.lastname: Belvisi
authors.forename: Cesare
authors.initials: C
authors.lastname: Casagrande
authors.forename: Roberto
authors.initials: R
authors.lastname: Fanelli
authors.forename: Leonardo
authors.initials: L
authors.lastname: Manzoni
authors.forename: Emilio
authors.initials: E
authors.lastname: Parisini
authors.forename: Umberto
authors.initials: U
authors.lastname: Piarulli
authors.forename: Elena
authors.initials: E
authors.lastname: Luison
authors.forename: Mariangela
authors.initials: M
authors.lastname: Figini
authors.forename: Antonella
authors.initials: A
authors.lastname: Tomassetti
authors.forename: Monica
authors.initials: M
authors.lastname: Civera
mesh_terms: D015820:Cadherins / Q000037:antagonists & inhibitors*; D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D057786:Peptidomimetics; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D015820:Cadherins; D008024:Ligands; D009842:Oligopeptides; D057786:Peptidomimetics; D054852:Small Molecule Libraries