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CH2. This order is individual for each DNA polymerase. It is interesting to mention that β,γ-CBr2 substituted dTTP is neither a substrate nor an inhibitor of DNA polymerase β. This specificity distinguishes DNA polymerase β from other DNA polymerases studied.
doi:10.1016/j.lfs.2007.01.049 
Copyright © 2007 Elsevier Inc. All rights reserved.
Epicatechin conjugated with fatty acid is a potent inhibitor of DNA polymerase and angiogenesis
Kiminori Matsubaraa, b, 
, 1, 
, Akiko Saitoc, Akira Tanakad, Noriyuki Nakajimae, Reiko Akagia, Masaharu Morif and Yoshiyuki Mizushinab, g
Received 28 August 2006;
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Abstract
Anti-cancer and anti-angiogenesis effects of green tea catechins have been demonstrated. It has been found that chemical modification of tea catechins improves their biological activities. We examined the chemical modification of epicatechin enhanced anti-cancer and anti-angiogenic effects. Epicatechin conjugated with fatty acid (acyl-catechin) strongly inhibited DNA polymerase activity, HL-60 cancer cell growth and angiogenesis. Epicatechin conjugated with palmitic acid ((2R,3R)-3′,4′,5,7-tetrahydroxyflavan-3-yl hexadecanoate, epicatechin-C16) was the strongest inhibitor in DNA polymerase α, β, λ and angiogenesis assays. Epicatechin-C16 also suppressed human endothelial cell (HUVEC) tube formation on reconstituted basement membrane, suggesting that it affected not only DNA polymerase activity but also the signal transduction pathways needed for the tube formation in HUVECs. These results suggest that acylation of epicatechin is an effective chemical modification to improve the anti-cancer activity of epicatechin.
Keywords: Angiogenesis; Aortic ring; Epicatechin; Endothelial cells; Fatty acid
Article Outline
- Introduction
- Materials and methods
- Materials
- Synthesis
- Synthesis of tetra-benzylated epicatechin
- General procedure for the esterification of benzylated flavan-3-ols
- General procedure for the hydrogenation of benzyl protecting group of acyl-epicatechins
- (2R,3R)-3′,4′,5,7-Tetra-O-benzylflavan-3-yl dodecanoate (2)
- (2R,3R)-3′,4′,5,7-Tetrahydroxyflavan-3-dodecanoate, epicatechin-C12
- (2R,3R)-3′,4′,5,7-Tetra-O-benzylflavan-3-yl tetradecanoate (3)
- (2R,3R)-3′,4′,5,7-Tetrahydroxyflavan-3-yl tetradecanoate, epicatechin-C14
- (2R,3R)-3′,4′,5,7-Tetra-O-benzylflavan-3-yl hexadecanoate (4)
- (2R,3R)-3′,4′,5,7-Tetrahydroxyflavan-3-yl hexadecanoate, epicatechin-C16
- DNA polymerase assays
- Cell culture and measurement of cell viability
- Ex vivo angiogenesis assay
- Endothelial cells
- HUVEC tube formation assay
- Statistical analysis
- Results
- Synthesis of 3-O-acylepicatechin derivatives
- Effects of acyl-epicatechin compounds on DNA polymerase activities
- Effects of acyl-epicatechin compounds on cancer cell growth
- Effects of acyl-epicatechin compounds on ex vivo angiogenesis
- Effect of epicatechin-C16 on HUVEC tube formation
- Discussion
- Acknowledgements
- References
; p < 0.01) is significantly different from control.
