title: Synthesis and biological studies of neopetrosiamides as inhibitors of cancer cell invasion.
abstract: The tricyclic peptides neopetrosiamides A and B, isolated from the marine sponge Neopetrosia sp., are potential antimetastatic agents that inhibit tumour cell invasion by both amoeboid and mesenchymal migration pathways. They differ in the stereochemistry of the methionine sulfoxide at position 24. Our previously reported syntheses using an orthogonal sulfur protection strategy established the critical connectivity of the three disulfide bonds. In this report, fifteen analogues of neopetrosiamide A and B, six which replace selected disulfide bonds and nine which replace the diastereomeric methionine sulfoxide, have been prepared using Fmoc solid-phase peptide chemistry. Disulfide replacement analogues were shown to lose activity, and only one of the methionine sulfoxide analogues retained full bioactivity in morphological studies.
authors: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors: Kaitlyn M
authors: KM
authors: Towle
authors: Jennifer L
authors: JL
authors: Chaytor
authors: Hongqiang
authors: H
authors: Liu
authors: Pamela
authors: P
authors: Austin
authors: Michel
authors: M
authors: Roberge
authors: Calvin D
authors: CD
authors: Roskelley
authors: John C
authors: JC
authors: Vederas
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C512184:neopetrosiamide A; C512185:neopetrosiamide B