Koshikamide B, a cytotoxic peptide lactone from a marine sponge Theonella sp.

Abstract

Koshikamide B (1) has been isolated from two separate collections of the marine sponge Theonella sp. as the major cytotoxic constituent. Koshikamide B is a 17-residue peptide lactone composed of six proteinogenic amino acids, two D-isomers of proteinogenic amino acids, seven N-methylated amino acids, and two unusual amino acid residues. The unusual amino acids are N(delta)-carbamoylasparagine and 2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid (AHPP); the former is first found as the constituent of peptides, whereas the latter is a new amino acid residue. The N-terminus of koshikamide B is blocked by a methoxyacetyl group. The structure of koshikamide B (1) has been determined by interpretation of spectral data and analysis of chemical degradation products. Koshikamide B (1) exhibits cytotoxicity against P388 murine leukemia cells and the human colon tumor (HCT-116) cell line with an IC50 value of 0.45 and 7.5 microg/mL, respectively.

• Authors: Takahiro Araki, Shigeki Matsunaga, Yoichi Nakao, Kazuo Furihata, Lyndon West, D John Faulkner, Nobuhiro Fusetani
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 73 Issue 20 Pg. 7889-94 (Oct 17 2008) ISSN: 1520-6904 [Electronic] United States
• PMID: 18811200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid
• Lactones
• N(delta)-carbamoylasparagine
• Oligopeptides
• Propionates
• Pyrrolidines
• koshikamide B
• Asparagine

Topics

• Animals
• Asparagine (analogs & derivatives, chemistry)
• Drug Screening Assays, Antitumor
• Humans
• Inhibitory Concentration 50
• Lactones (chemistry)
• Mice
• Oligopeptides (chemistry, toxicity)
• Propionates (chemistry)
• Pyrrolidines (chemistry)
• Theonella (chemistry, metabolism)
• Tumor Cells, Cultured