13-Deoxytedanolide, a marine sponge-derived antitumor macrolide, binds to the 60S large ribosomal subunit.
13-Deoxytedanolide is a potent antitumor macrolide isolated from the marine sponge Mycale adhaerens. In spite of its remarkable activity, the mode of action of 13-deoxytedanolide has not been elucidated. [11-3H]-(11S)-13-Deoxydihydrotedanolide derived from the macrolide was used for identifying the target molecule from the yeast cell lysate. Fractionation of the binding protein revealed that the labeled 13-deoxytedanolide derivative strongly bound to the 80S ribosome as well as to the 60S large subunit, but not to the 40S small subunit. In agreement with this observation, 13-deoxytedanolide efficiently inhibited the polypeptide elongation. Interestingly, competition studies demonstrated that 13-deoxytedanolide shared the binding site on the 60S large subunit with pederin and its marine-derived analogues. These results indicate that 13-deoxytedanolide is a potent protein synthesis inhibitor and is the first macrolide to inhibit the eukaryotic ribosome.
Nishimura
Shinichi
S
Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Matsunaga
Shigeki
S
Yoshida
Minoru
M
Hirota
Hiroshi
H
Yokoyama
Shigeyuki
S
Fusetani
Nobuhiro
N
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism*; D001667:Binding, Competitive; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D011161:Porifera; D011485:Protein Binding; D021122:Protein Subunits; D012269:Ribosomal Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
C409106:13-deoxytedanolide; D000970:Antineoplastic Agents; D018942:Macrolides; D021122:Protein Subunits; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins