Abstract
It has been shown that ethyl 5-amino-l,2-dihydro-2-methyl-3-phenyl pyrido (3,4-b)pyrazin-7-yl carbamate (NSC 370147) inhibits microtubule formation, that this racemic compound binds to tubulin at or near the colchicine site, and that it enhances the binding of Vincristine to tubulin1. It appeared of interest to evaluate the activity of the R-enantiomer (NSC 613863) and the S-enantiomer (NSC 613862, CI 980). Hence, their interactions were examined at molecular level. Furthermore, we compared the binding properties of these new compounds to those of colchicine and colchicine analogues, which are firmly established. The influence of chirality on the polymerization of microtubule proteins and tubulin is also discussed.
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References
Bowdon, B.J., Waud, W.R., Wheeler, G.P., Hain, R.,Dansby,L., and Temple, C.Jr., 1987,Comparison of l-2-dihydropyrido[3,4-b]pyrazines(l -deaza-7-8-dihydro-pteridines) with several other inhibitors of mitosis. Cancer Res. 47:1621–1626.
David-Pfeuty, Th., Simon, C., and Pantaloni, D., 1979,Effect of antimitotic drugs on tubulin GTPase activity and self assembly. J. Biol. Chem. 254:11696–11702.
Himes, R.H., Kersey, K.N., Heller-Bettinger, I., and Samson,F., 1976,Action of the vinca alkaloids vincristine, vinblastine and desacetyl vinblastineamide on microtubules in vitro. Cancer Res. 36:3798–3802.
Andreu, J.M., Gorbunoff, J.M., Lee, J.C., and Timasheff,S.N., 1984,Interaction of tubulin with bifunctionnal colchicine analogues on equilibrium study. Biochemistry 23:1742–1753.
Garland, D.L, 1978, Kinetics and mechanism of colchicine binding to tubulin : evidence for ligand-induced conformational change. Biochemistry 17:4266–4272.
Cortese, F., Battacharyya, B., and Wolff, J., 1977,Podophyllotoxin as a probe for the colchicine binding site of tubulin. J. Biol. Chem. 252:1134–1140.
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© 1993 Springer Science+Business Media New York
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Leynadier, D. et al. (1993). Tubulin Binding Properties of Two Chiral Isomers with 1-Deaza-7, 8-Dihydropteridine Structure. In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_94
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DOI: https://doi.org/10.1007/978-1-4615-2960-6_94
Publisher Name: Springer, Boston, MA
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Online ISBN: 978-1-4615-2960-6
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