title: Aza-cycloisodityrosine analogue of RA-VII, an antitumor bicyclic hexapeptide.
abstract: An aza-cycloisodityrosine analogue of RA-VII, 3, was designed and synthesized. The key aza-cycloisodityrosine unit was prepared by copper(II)-acetate-mediated intramolecular phenylamine/arylboronic acid coupling of dipeptide followed by connection with the tetrapeptide segment to afford a hexapeptide. Subsequent macrocyclization of the hexapeptide with EDC · HCl and HOOBt under dilute conditions gave 3. Analogue 3 showed significant cytotoxic activity against human promyelocytic leukemia HL-60 cells and human colon carcinoma HCT-116 cells, but its activity was weaker than that of parent peptide RA-VII (1).
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hitotsuyanagi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miyazawa
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Hinosawa
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hasuda
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeya
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001372:Aza Compounds / Q000737:chemistry; D018360:Crystallography, X-Ray; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045470:Rubia / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001372:Aza Compounds; D010455:Peptides; D010456:Peptides, Cyclic; C018234:bouvardin; D014443:Tyrosine; C035129:isodityrosine; C043548:RA VII
keywords: Aza-cycloisodityrosine; Bouvardin; Cytotoxicity; RA-VII; Rubia cordifolia