title: Chemical synthesis and biological activity of the neopetrosiamides and their analogues: revision of disulfide bond connectivity.
abstract: Neopetrosiamides A and B (2) from the marine sponge Neopetrosia sp. are two diastereomeric tricyclic peptides that inhibit tumor cell invasion associated with metastasis. The reported structures were chemically synthesized using solid-phase peptide synthesis and sequential stepwise disulfide bond formation in solution. The disulfide bond connectivity of the originally proposed structures was revised and confirmed by chemical synthesis together with a combination of HPLC analysis, disulfide mapping, and biological activity testing. This methodology was also utilized to generate analogues containing methionine or norleucine in place of the methionine sulfoxide at position 24. Compounds 4 and 6 demonstrated potent bioactivity comparable to that of the parent peptides.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Liu
authors.forename: Marc A
authors.initials: MA
authors.lastname: Boudreau
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Randy M
authors.initials: RM
authors.lastname: Whittal
authors.forename: Pamela
authors.initials: P
authors.lastname: Austin
authors.forename: Calvin D
authors.initials: CD
authors.lastname: Roskelley
authors.forename: Michel
authors.initials: M
authors.lastname: Roberge
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Andersen
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*
chemical_list: D004220:Disulfides; D010456:Peptides, Cyclic; C512184:neopetrosiamide A; C512185:neopetrosiamide B