Abstract
Alkyltransferases catalyze the reaction of various cellular nucleophiles with an electrophilic carbon adjacent to electron-deficient trivalent sulfur. In the case of methyltransferases, nucleophilic attack is at the methyl group of S-adenosylmethionine (AdoMet), whereas with the aminopropyltransferases, attack is at the less reactive aminopropyl methylene group of S-adenosyl(3-methylthio)-propylamine (decarboxylated AdoMet, dcAdoMet). Although nucleophilic attack at sp3 carbon is one of the most extensively studied reactions in organic chemistry, much less is known about the corresponding biochemical reactions catalyzed by the alkyltransferases. Our own mechanistic studies have focused on three areas of investigation: catalysis of non-enzymatic model reactions, kinetics of enzyme-catalyzed reactions, and stereochemistry of enzyme-catalyzed reactions. Since this research is the basis for our inhibitor design and synthesis work, it will be reveiwed briefly here.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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
Anderson, G. L., Bussolotti, D. L., and Coward, J. K. (1981) J. Med. Chem. 24, 1271–1277.
Benghiat, E. amd Crooks, P. A. (1983) J. Med. Chem. 26, l470–l477.
Borchardt, R. T. (1973) J. Med. Chem. l6, 377–382.
Coward, J. K. (1980) in Molecular Action and Targets for Cancer Chemotherapeutic Agents (Sartorelli, A. C., Lazo, J., and Bertino, J. R., Eds.) p. 253–263, Academic Press, New York.
Coward, J. K. (1982) Ann. Rept. Med. Chem. 17, 253–259.
Coward, J. K., Anderson, G. L., and Tang, K.-C. (1983a) Methods Enzymol 94, 286–294.
Coward, J. K., Chaudhari, P. R., Kwiat, M. A. and Hluboky,M. (1983b) Fed. Proc. 42, 1892 (Abstract).
Coward, J. K., Motola, N. C., and Moyer, J. D. (1977) J. Med. Chem. 20, 500–505.
Coward, J. K., Slisz, E. P., and Wu, F. Y_H. (1973) Biochemistry 12, 2291–2297.
Floss, H. G. and Tsai, M.-D. (1979) Adv. Enzymol. 50, 243– 302.
Golding, B. T. and Nassereddin, I. K. (1982) J. Amer. Chem.Soc. 104, 5815–5817.
Guldberg, H. C. and Marsden, C. A. (1975) Pharmacol. Rev. 27, 135–206.
Heller, J. S., Canellakis, E. S., Bussolotti, D. L., and Coward, J. K. (1975) Biochim. Biophys. Acta 403, 197–207.
Hibasami, H., Borchardt, R. T., Chen, S. Y., Coward, J. K., and Pegg, A. E. (1980) Biochem. J. 187, 419–428.
Knipe, J. O. and Coward, J. K. (1979) J. Amer. Chem. Soc. 101, 4339–4348.
Knipe, J. O., Vasquez, P. J., and Coward, J. K. (1982)J. Amer. Chem. Soc. 104, 3202–3209.
Lyga, J. W. and Secrist, J. A. (1983) J. Org. Chem. 48, 1982–1988.
Orr, G. R., Kullberg, D., and Coward, J. K. (1984) Biochemistry 23, 3350–3351 (Abstract).
Pegg, A. E., Bitonti, A. J., McCann, P. P., and Coward, J. K. (1983) FEBS Lett. 155, 192–196.
Pegg, A. E., Tang, K.-C., and Coward, J. K. (1982) Biochemistry 21, 5082–5089.
Pontoni, G., Coward, J. K., Orr, G., and Gould, S. J.(1983) Tetrahedron Lett. 24, 151–154.
Raina, A., Hyvonen, T., Eloranta, T., Vortilainen, M., Samejima, K., and Yamanoha, B. (1984) Biochem. J. 219, 991–1000.
Rivett, A. J. and Roth, J. A. (1982) Biochemistry 21, 1740– 1742.
Tang, K.-C., Mariuzza, R., and Coward, J. K. (198l) J. Med.Chem. 24, 1277–1284.
Tang, K.-C., Pegg, A. E., and Coward, J. K. (1980) Biochem.Biophys. Res. Commun. 96, 1371–1377.
Woodard, R. W., Tsai, M.-D., Floss, H. G., Crooks, P. A., and Coward, J. K. (1980) J. Biol. Chem. 255, 9124–9127.
Zappia, V., Cacciapuoti, G., Pontoni, G., and Oliva, A. (1980) J. Biol. Chem. 255, 7276–7280.
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
Coward, J.K. (1986). Mechanism-Based Inhibitors of Alkyltransferases. 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_36
Download citation
DOI: https://doi.org/10.1007/978-1-4612-5012-8_36
Publisher Name: Humana Press
Print ISBN: 978-1-4612-9398-9
Online ISBN: 978-1-4612-5012-8
eBook Packages: Springer Book Archive