title: Rescuing biological activity from synthetic phakellistatin 19.
abstract: Phakellistatins is one of the families of Pro-rich cyclic peptides whose synthetic counterparts have revealed cytotoxicities that differ greatly from those displayed by their corresponding natural ones. This is also the case of the last member isolated from this family, phakellistatin19, an octacyclopeptide containing three Pro moieties and a high percentage of apolar residues. Exhaustive NMR studies on the synthetic and natural phakellistatin 19 have been performed in order to find a plausible explanation for this intriguing behavior. Moreover, taking advantage of phakellistatin's framework, analogues with different cis/trans geometry at the key prolyl peptide bonds were designed, covering a promising conformational space that could not be reached by the natural peptide. By introduction of proline surrogates (Ψ(Me,Me)pro residues) in phakellistatin 19, which effectively increases the percentage of cis conformation in the final peptides, this translates into enhanced biological activity, therefore "rescuing" an otherwise inactive cyclopeptide.
authors.affiliation: Institute for Research in Biomedicine-Barcelona , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pelay-Gimeno
authors.forename: Alessandra
authors.initials: A
authors.lastname: Meli
authors.forename: Judit
authors.initials: J
authors.lastname: Tulla-Puche
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D010456:Peptides, Cyclic; C095625:phakellistatin 10; D011392:Proline