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Inhibitory action of conjugated C 18 ‐fatty acids on DNA polymerases and DNA topoisomerases
Author(s) -
Mizushina Yoshiyuki,
Tsuzuki Tsuyoshi,
Eitsuka Takahiro,
Miyazawa Teruo,
Kobayashi Kanako,
Ikawa Hiroshi,
Kuriyama Isoko,
Yonezawa Yuko,
Takemura Masaharu,
Yoshida Hiromi,
Sakaguchi Kengo
Publication year - 2004
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-004-1319-y
Subject(s) - dna , conjugated system , topoisomerase , dna polymerase , biochemistry , enzyme , chemistry , stereochemistry , conjugated linoleic acid , polymerase , fatty acid , linoleic acid , organic chemistry , polymer
We reported previously that unsaturated linear‐chain FA of the cis ‐configuration with a C 18 ‐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 C 18 ‐FA on mammalian DNA polymerases and DNA topoisomerases as compared with normal unsaturated FA. The conjugated α‐eleostearic acid (18∶3Δ9 c , 11 t , 13 t ) 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 C 18 ‐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.