TY - JOUR
T1 - Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases
AU - Kimura, Takuma
AU - Takeuchi, Toshifumi
AU - Kumamoto-Yonezawa, Yuko
AU - Ohashi, Eiji
AU - Ohmori, Haruo
AU - Masutani, Chikahide
AU - Hanaoka, Fumio
AU - Sugawara, Fumio
AU - Yoshida, Hiromi
AU - Mizushina, Yoshiyuki
N1 - Funding Information:
This work was supported in part by a Grant-in-aid for Kobe-Gakuin University Joint Research (A), and ‘Academic Frontier’ Project for Private Universities: matching fund subsidy from MEXT (Ministry of Education, Culture, Sports, Science and Technology), 2006–2010 (Y.M. and H.Y.). Y.M. acknowledges a Grant-in-Aid for Young Scientists (A) (No. 19680031) from MEXT, Grants-in-Aid from The Salt Science Research Foundation, No. 08S3 (Japan), and a Grant from the Industrial Technology Research Program from NEDO (Japan).
PY - 2009/3/1
Y1 - 2009/3/1
N2 - Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols η, ι and κ), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol ι activity was most strongly inhibited by compounds 1 and 2, with IC50 values of 19.8 and 32.5 μM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ε) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.
AB - Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols η, ι and κ), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol ι activity was most strongly inhibited by compounds 1 and 2, with IC50 values of 19.8 and 32.5 μM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ε) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.
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U2 - 10.1016/j.bmc.2009.01.064
DO - 10.1016/j.bmc.2009.01.064
M3 - Article
C2 - 19223184
AN - SCOPUS:61349196981
VL - 17
SP - 1811
EP - 1816
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 5
ER -