TY - JOUR
T1 - Inhibitory action of conjugated C18-fatty acids on DNA polymerases and DNA topoisomerases
AU - Mizushina, Yoshiyuki
AU - Tsuzuki, Tsuyoshi
AU - Eitsuka, Takahiro
AU - Miyazawa, Teruo
AU - Kobayashi, Kanako
AU - Ikawa, Hiroshi
AU - Kuriyama, Isoko
AU - Yonezawa, Yuko
AU - Takemura, Masaharu
AU - Yoshida, Hiromi
AU - Sakaguchi, Kengo
N1 - Funding Information:
This work was partly supported by a Grant-in-Aid for Kobe Gakuin University Joint Research (B) (Y.M. and H.Y.). Y.M. acknowledges Grants-in-Aid from the Hyogo Science and Technology Association, The Japan Food Chemical Research Foundation, and Grant-in-Aid 14780466 for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
PY - 2004/10
Y1 - 2004/10
N2 - We reported previously that unsaturated linear-chain FA of the cis-configuration with a C18-hydrocarbon chain such as linoleic acid (18:2Δ9c, 12c) could potently inhibit the activities of mammalian DNA polymerases and DNA topoisomerases, but their saturated forms could not. There are chemically two classes of unsaturated FA, normal and conjugated, but only the conjugated forms show potent antitumor activity. In this report, we study the inhibitory effects of chemically synthesized conjugated C18-FA on mammalian DNA polymerases and DNA topoisomerases as compared with normal unsaturated FA. The conjugated α-eleostearic acid (18:3Δ9c, 11t, 13t) was the strongest of all the FA tested. For the inhibition, the conjugated form is crucially important. The energy-minimized 3-D structures of the FA were calculated, and both a length of less than 20 Å and a width of 8.13-9.24 Å in the C18-FA structure were found to be important for enzyme inhibition. The 3-D structure of the active site of both DNA polymerases and topoisomerases must have had a pocket to join α-eleostearic acid, and this pocket was 12.03 Å long and 9.24 Å wide.
AB - We reported previously that unsaturated linear-chain FA of the cis-configuration with a C18-hydrocarbon chain such as linoleic acid (18:2Δ9c, 12c) could potently inhibit the activities of mammalian DNA polymerases and DNA topoisomerases, but their saturated forms could not. There are chemically two classes of unsaturated FA, normal and conjugated, but only the conjugated forms show potent antitumor activity. In this report, we study the inhibitory effects of chemically synthesized conjugated C18-FA on mammalian DNA polymerases and DNA topoisomerases as compared with normal unsaturated FA. The conjugated α-eleostearic acid (18:3Δ9c, 11t, 13t) was the strongest of all the FA tested. For the inhibition, the conjugated form is crucially important. The energy-minimized 3-D structures of the FA were calculated, and both a length of less than 20 Å and a width of 8.13-9.24 Å in the C18-FA structure were found to be important for enzyme inhibition. The 3-D structure of the active site of both DNA polymerases and topoisomerases must have had a pocket to join α-eleostearic acid, and this pocket was 12.03 Å long and 9.24 Å wide.
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U2 - 10.1007/s11745-004-1319-y
DO - 10.1007/s11745-004-1319-y
M3 - Article
C2 - 15691019
AN - SCOPUS:19944427269
SN - 0024-4201
VL - 39
SP - 977
EP - 983
JO - Lipids
JF - Lipids
IS - 10
M1 - L9577
ER -