Description
(+)-
Aphidicolin is a natural tetracyclic diterpene first isolated from the fungus
C. aphidicola and shown to have antiviral activity against herpes simplex. In eukaryotic cells, it is a cell-
permeable, reversible inhibitor of DNA replication, specifically blocking the activity of DNA polymerases α, δ, and ε when used at low micromolar levels. Aphidicolin can be used, at 3 μM, to arrest cells in G
1/S phase or to increase gene amplification frequency.
Chemical Properties
White crystal
Uses
A DNA polymerase inhibitor. Blocks the cell cycle at the early S-phase
Uses
Aphidicolin is a tetracyclic diterpene antibiotic isolated from fungi, notably Cephalosporium, Nigrospora, Harziella and Phoma. Aphidicolin has antibiotic, antiviral and antimitotic properties, blocking the cell cycle at early S-phase. This property has been used to synchronise cell division and is useful as a tool in cell differentiation research. Aphidicolin is a reversible inhibitor of DNA replication by inhibiting selected DNA polymerases. Aphidicolin induces apoptosis, prolongs the half-life of DNA methyltransferase, is active against Leishmania parasites and acts synergistically with the antitumour agents, vincristine and doxorubicin.
Uses
(+)-Aphidicolin is a naturally occurring tetracyclic diterpene with potential antiviral and antimitotical properties.
Definition
ChEBI: A tetracyclic diterpenoid that has an tetradecahydro-8,11a-methanocyclohepta[a]naphthalene skeleton with two hydroxymethyl substituents at positions 4 and 9, two methyl substituents at positions 4 and 11b and two hydroxy substituents at positi
ns 3 and 9. An antibiotic with antiviral and antimitotical properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication.
General Description
A cell-permeable tetracyclic diterpene antibiotic. Cell synchronization agent. Blocks the cell cycle at the early S-phase. Specific inhibitor of DNA polymerase α and δ in eukaryotic cells and in some viruses of animal origin. Potentiates apoptosis induced by arabinosyl nucleosides in leukemia cell lines. Also induces apoptosis in HeLaS3 cells, but inhibits vincristine-induced apoptosis in the p53-negative human prostate cancer cell line PC-3.
Biochem/physiol Actions
Cell permeable: yes
Background
Aphidicolin is a tetracyclic diterpenoid first produced by the fungus Cephalosporium aphidicola. This antibiotic is a potent inhibitor of cellular deoxyribonucleic acid synthesis by targeting α, ε, and δ DNA polymerases in eukaryotic cells lines with little to no effect on β or γ DNA polymerases. Studies have shown that Aphidicolin specifically binds to α DNA polymerase, resulting in the formation of a pol α-DNA-aphidicolin ternary complex that blocks DNA replication. The uses for this compound include synchronized cells at the G1/S boundary and increased gene amplification.
References
[1] J SYVÄOJA. DNA polymerases alpha, delta, and epsilon: three distinct enzymes from HeLa cells.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1990, 87 17: 6664-6668. DOI:
10.1073/pnas.87.17.6664[2] LENORE URBANI Robert T S Steven W Sherwood. Dissociation of Nuclear and Cytoplasmic Cell Cycle Progression by Drugs Employed in Cell Synchronization[J]. Experimental cell research, 1995, 219 1: Pages 159-168. DOI:
10.1006/excr.1995.1216[3] KATSUJI KUWAKADO. Aphidicolin potentiates apoptosis induced by arabinosyl nucleotides in human myeloid leukemia cell lines[J]. Biochemical pharmacology, 1993, 46 11: Pages 1909-1916. DOI:
10.1016/0006-2952(93)90631-6[4] D X YIN R T S. Inhibition of apoptosis by overexpressing Bcl-2 enhances gene amplification by a mechanism independent of aphidicolin pretreatment.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1996, 93 8: 3394-3398. DOI:
10.1073/pnas.93.8.3394
