title: Synthesis of [Tyr-5-Ψ(CH2NMe)-Tyr-6]RA-VII, a reduced peptide bond analogue of RA-VII, an antitumor bicyclic hexapeptide.
abstract: A reduced peptide bond analogue of RA-VII, [Tyr-5-Ψ(CH(2)NMe)-Tyr-6]RA-VII (3), was designed and synthesized. The key reduced cycloisodityrosine unit was prepared by reduction of the cycloisodityrosine derived from natural RA-VII, followed by connection with the tetrapeptide segment to afford a hexapeptide. Subsequent macrocyclization of the hexapeptide with FDPP under dilute conditions gave 3. Analogue 3 showed cytotoxic activity against P-388 cells, but its activity was much weaker than that of parent peptide RA-VII.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hasuda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hitotsuyanagi
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Shinada
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeya
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C574956:(Tyr-5-psi(CH2NMe)-Tyr-6)RA-VII; D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C043548:RA VII