Biological activity, structural features, and synthetic studies of (-)-ternatin, a potent fat-accumulation inhibitor of 3T3-L1 adipocytes

Abstract

A series of studies, including preliminary screening, isolation, structure determination, synthesis, and biological evaluation, of (-)-ternatin (1) are described. A highly N-methylated cyclic heptapeptide isolated from the mushroom Coriolus versicolor, 1 shows an inhibitory effect on fat accumulation by 3T3-L1 murine adipocytes (EC50 = 0.02 microg mL(-1)). Detailed analysis of 1D and 2D NMR spectra, as well as amino acid analysis, suggested four stereoisomers as candidates for 1. For the complete structural elucidation of 1, chemical syntheses were carried out by solid-phase peptide synthesis. By comparing the spectroscopic data for the natural product with the data for the synthetic stereoisomers, the structure of 1 was confirmed to be cyclo[D-allo-Ile1-L-(NMe)Ala2-L-(NMe)Leu3-L-Leu4-L-(NMe)Ala5-D-(NMe)Ala6-(2R,3R)-3-hydroxy-Leu7].