Biological activity, structural features, and synthetic studies of (-)-ternatin, a potent fat-accumulation inhibitor of 3T3-L1 adipocytes.
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].
Shimokawa
Kenichiro
K
Department of Chemistry, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8602, Japan.
Mashima
Itsuka
I
Asai
Akiko
A
Ohno
Tomohiro
T
Yamada
Kaoru
K
Kita
Masaki
M
Uemura
Daisuke
D
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000363:Agaricales / Q000737:chemistry; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005223:Fats / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013696:Temperature
D005223:Fats; D010456:Peptides, Cyclic; D010936:Plant Extracts; C085773:ternatin heptapeptide