Chemical synthesis and biological activity of the neopetrosiamides and their analogues: revision of disulfide bond connectivity.
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.
Liu
Hongqiang
H
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Boudreau
Marc A
MA
Zheng
Jing
J
Whittal
Randy M
RM
Austin
Pamela
P
Roskelley
Calvin D
CD
Roberge
Michel
M
Andersen
Raymond J
RJ
Vederas
John C
JC
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*
D004220:Disulfides; D010456:Peptides, Cyclic; C512184:neopetrosiamide A; C512185:neopetrosiamide B