Abstract
Neplanocin A [(-)-9-[trans-2, trans-3-dihydroxy-4-(hydroxymethyl) cyclopent-4-enyl] adenine] (Figure 1) is a cyclopentenyl analog of adenosine which has been isolated from the culture filtrate of the microorganism Ampullariella regularis (Yaginuma et al., 1980, 1981; Hayashi et al., 1981). Despite having minimal antibacterial and antifungal activity, this novel antibiotic was initially observed to be cytotoxic at 0.2 µg/ml against cultured L5178Y lymphoma cells (Yaginuma et al., 1981). It also exhibited significant antitumor activity in mice bearing L1210 leukemia, increasing the life span by 120% at 5 mg/kg/day (Tsujino et al., 1980; Yaginuma et al., 1981).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aarbakke, J., Gordon, R.K., Cross, A.S., Miura, G.A. and Chiang, P.K. (1985) Fed. Proc. 44. 464, abst.#313.
Bartel, R.L. and Borchardt, R.T. (1985) Anal. Biochem. 149.191–196.
Borchardt, R.T. (1979) J. Amer. Chem. Soc. 101.458–463.
Borchardt, R.T. and Pugh, C.S.G. (1979) in Transmethylation (Usdin, E., Borchardt, R.T. and Creveling, C.R., eds.) pp. 197–206, Elsevier/North-Holland, New York.
Borchardt, R.T., Keller, B.T. and Patel-Thombre, U. (1984) J. Biol. Chem. 259, 4353–4358.
De Clercq, E. (1985) Antimicrob. Agents Chemother. 28. 84–89.
De Clercq, E. and Cools, M. (1985) Biochem. Biophys. Res. Commun. 129. 306–311.
De Clercq, E. and Montgomery, J.A. (1983) Antiviral Res. 3,17–24.
De Clercq, E., Descamps, J., De Somer, P. and Holy, A. (1978) Science 200. 563–565.
Glazer, R.I. and Knode, M.C. (1984) J. Biol. Chem. 259.12964–12969.
Hayashi, M., Yaginuma, S., Yishioka, H. and Nakatsu, K. (1981) J. Antibiot. (Tokvo) 34, 675–680.
Hohman, R.J., Guitton, M.C. and Vernon, M. (1985) Proc. Natl. Acad. Sei. USA. 82, 4578–4581.
Keller, B.T. and Borchardt, R.T. (1983) Fed. Proc. 42. 2139, abst.#2230.
Keller, B.T. and Borchardt, R.T. (1984) Biochem. Biophys. Res. Commun. 120. 131–137.
Keller, B.T., Clark, R.S., Pegg, A.E. and Borchardt, R.T. (1985) Mol. Pharmacol, 28, 364–370.
Ramakrishnan, V. and Borchardt, R.T. (1984) Fed. Proc. 43. 1556, abst. #814.
Rice, A.P. and Roberts, B.E. (1983) J. Virology 47. 529–539.
Saunders, P.P., Tan, M.T. and Robins, R.K. (1985) Biochem. Pharmacol. 34, 2749–2754.
Tsujino, M., Yaginuma, S., Fujii, T., Hayano, K., Matsudo, T., Watanabe, T. and Abe, J. (1980) in Current Chemotherapy and Infectious Disease. Proceedings of the 11 th International Congress of Chemotherapy (Nelson, J.D. and Grassi, C., eds.) Vol. 2, pp. 1559–1561, The American Society for Microbiology, Washington, DC.
Whaun, J.M., Miura, G.A., Brown, N.D., Gordon, R.K. and Chiang, P.K.. (1985) Fed. Proc. 44. 499, abst.#516.
Yaginuma, S., Tsujino, M., Muto, N., Otani, M., Hayashi, M., Ishimura, F., Fujii, T., Watanabe, S., Matsuda, T., Watanabe, T. and Abe, J. (1980) in Current Chemotherapy and Infectious Disease. Proceedings of the 11 th International Congress of Chemotherapy (Nelson, J.D. and Grassi, C., eds.) Vol. 2, pp. 1558–1559, The American Society for Microbiology, Washington, DC.
Yaginuma, S., Muto, N., Tsujino, M., Sudate, Y., Hayashi, M. and Otani, M. (1981) J. Antibiot. (Tokyo) 34, 359–366.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 The Humana Press Inc.
About this chapter
Cite this chapter
Keller, B.T., Borchardt, R.T. (1986). Metabolism and Mechanism of Action of Neplanocin A — A Potent Inhibitor of S-Adenosylhomocysteine Hydrolase. In: Borchardt, R.T., Creveling, C.R., Ueland, P.M. (eds) Biological Methylation and Drug Design. Experimental Biology and Medicine, vol 12. Humana Press. https://doi.org/10.1007/978-1-4612-5012-8_32
Download citation
DOI: https://doi.org/10.1007/978-1-4612-5012-8_32
Publisher Name: Humana Press
Print ISBN: 978-1-4612-9398-9
Online ISBN: 978-1-4612-5012-8
eBook Packages: Springer Book Archive