Synthesis of biotinylated xestoquinone that retains inhibitory activity against Ca2+ ATPase of skeletal muscle myosin.
Xestoquinone isolated from a marine sponge binds to skeletal muscle myosin and inhibits its Ca(2+) ATPase activity. In this study, we first examined xestoquinone and its analogues to assess the relationships between structure and myosin Ca(2+) ATPase inhibitory activity. On the basis of the resultant data, we then designed a biotinylated xestoquinone analogue. Xestoquinone and its analogues were derived from extracts of the marine sponge Xestospongia sapra. Four xestoquinone analogues with a quinone structure significantly inhibited Ca(2+) ATPase activity. In contrast, four xestoquinone analogues in which the quinone structure was converted to a quinol dimethyl ether did not inhibit Ca(2+) ATPase activity. This suggests that the quinone moiety is essential for inhibitory activity. Then, we synthesized a biotinylated xestoquinone in which a biotin tag was introduced to a site far from the quinone moiety, and this molecule exhibited stronger inhibitory activity than that of xestoquinone. This biotinylated xestoquinone could be useful as a probe in studies of the xestoquinone-myosin binding mode.
Nakamura
Mitsuhiro
M
Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, 464-8601, Nagoya, Japan.
Kakuda
Takahiko
T
Oba
Yuichi
Y
Ojika
Makoto
M
Nakamura
Hideshi
H
D000818:Animals; D001665:Binding Sites; D019921:Biotinylation; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006873:Hydroquinones / Q000737:chemistry; D008956:Models, Chemical; D011809:Quinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D024744:Skeletal Muscle Myosins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D011809:Quinones; C068501:xestoquinone; D024744:Skeletal Muscle Myosins; D000252:Calcium-Transporting ATPases