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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

A family of depsi-peptide fungal metabolites, as selective and competitive human tachykinin receptor (NK2) antagonists: fermentation, isolation, physico-chemical properties, and biological activity.

Four tachykinin (NK2) receptor inhibitors, SCH 378161 (1), SCH 217048 (2), SCH 378199 (3), and SCH 378167 (4) were isolated from the fermentation broth of a taxonomically unidentified fungus. These compounds were separated from the fermentation broth by ethyl acetate extraction. Purification and separation of the individual compounds were achieved by NK2 assay-guided fractionation using gel filtration, reverse phase chromatography and HPLC. They were identified to be a family of depsipeptides by spectroscopic and degradation studies. Compounds 1 and 3 contain proline and differ as an amide and acid whereas 2 and 4 contain pipecolic acid and differ in being an amide and acid. All of these compounds contain an identical hydroxy acid. They are selective NK2 inhibitors with Ki values ranging from 27-982 nM and demonstrate no activity at 10 microM in the NK1 and NK3 assays. In addition, compounds 1 and 2 inhibited NKA-induced increases in the concentration of intracellular Ca2+, [Ca2+]i, in a CHO cell expressing the human NK2 receptor; this inhibition was competitive in nature with pA2 values of 7.2 and 7.5, respectively. These data demonstrate that these natural products are selective and competitive receptor antagonists of the human NK2 receptor.[1]

References

  1. A family of depsi-peptide fungal metabolites, as selective and competitive human tachykinin receptor (NK2) antagonists: fermentation, isolation, physico-chemical properties, and biological activity. Hedge, V.R., Puar, M.S., Dai, P., Pu, H., Patel, M., Anthes, J.C., Richard, C., Terracciano, J., Das, P.R., Gullo, V. J. Antibiot. (2001) [Pubmed]
 
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