title: Structure-activity relationship of kahalalide F synthetic analogues.
abstract: Kahalalide F (KF) is a natural product currently under phase II clinical trials. Here, we report the solid phase synthesis of 132 novel analogues of kahalalide F and their in vitro activity on a panel of up to 14 cancer cell lines. The structure-activity relationship of these analogues revealed that KF is highly sensitive to backbone stereotopical modification but not to side chain size modification. These observations suggest that this compound has a defined conformational structure and also that it interacts with chiral compounds through its backbone and not through its side chains. The N-terminal aliphatic acid appears to be a hydrophobic buoy in a membrane-like environment. Moreover, significant improvement of the in vitro activity was achieved.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Josep Samitier 1, 08028 Barcelona, Spain.
authors.forename: José C
authors.initials: JC
authors.lastname: Jiménez
authors.forename: Angel
authors.initials: A
authors.lastname: López-Macià
authors.forename: Carol
authors.initials: C
authors.lastname: Gracia
authors.forename: Sonia
authors.initials: S
authors.lastname: Varón
authors.forename: Marta
authors.initials: M
authors.lastname: Carrascal
authors.forename: Josep M
authors.initials: JM
authors.lastname: Caba
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
authors.forename: Andrés M
authors.initials: AM
authors.lastname: Francesch
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuevas
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047630:Depsipeptides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; C097897:kahalalide F