Design and synthesis of FAJANU: a de novo C(2) symmetric cyclopeptide family.
A novel cyclic peptide has been designed from several potent marine cytotoxic peptides, including IB-01212, luzopeptin, triostin, and thiocoraline. The FAJANU scaffold maintains C 2 symmetry, cyclic structure, and the construction of aromatic and aliphatic character at the N- and C-terminal extremes. A first six-member family was previously synthesized and evaluated biologically. Several analogues presented greater activity than IB-01212. Furthermore, on the basis of the most active candidate, we have performed a more exhaustive synthetic and structural analysis: (i) structure-activity relationship provided clues about the key elements in the framework, (ii) NMR assignment confirmed C 2 symmetry, and (iii) confocal images revealed its penetration and cellular localization.
Garcia-Martin
Fayna
F
Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, Barcelona, Spain.
Cruz
Luis J
LJ
Rodriguez-Mias
Ricard A
RA
Giralt
Ernest
E
Albericio
Fernando
F
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic