Mechanism of Interaction of Vinca Alkaloids with Tubulin: Catharanthine and Vindoline.
IR@CFTRI: CSIR-Central Food Technological Research Institute, Mysore
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http://ir.cftri.com/13547/
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| Title |
Mechanism of Interaction of Vinca Alkaloids with Tubulin: Catharanthine and
Vindoline.
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| Creator |
Prakash, V.
Timasheff, S. N. |
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| Subject |
10 Plants
01 Alkaloid Biochemistry |
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| Description |
The interactions of the vinca alkaloid drugs catharanthine and vindoline with tubulin have been
investigated and compared with those of vinblastine and vincristine. Both drugs were found to be less effective
in bringing about the inhibition of tubulin self-assembly into microtubules than vincristine and vinblastine,
the drug to protein molar ratio required being 3 orders of magnitude greater. An analytical ultracentrifuge
study has shown that catharanthine can induce the self-association of tubulin into linear indefinite polymers
with an efficacy that is 75% that of vinblastine or vincristine, the intrinsic dimerization constant for the
liganded protein being K2 N 1 X lo5 M-l. The effect of vindoline was marginally detectable. Binding studies
of catharanthine using the gel batch and fluorescence perturbation techniques showed a polymerization-linked
binding of one catharanthine molecule per tubulin 0-0 dimer with a binding constant of (2.8 f 0.4) X lo3
M-’ , For vindoline, binding to tubulin was marginally detectable by fluorescence spectroscopy, although
addition of vindoline to tubulin did generate a difference spectrum. It was concluded that the binding of
vinblastine/vincristine to tubulin and its consequences are determined by the interaction of the indole part
of catharanthine with tubulin, the role of vindoline being that of an anchor.
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| Date |
1991
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| Type |
Article
PeerReviewed |
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| Format |
pdf
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| Language |
en
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| Identifier |
http://ir.cftri.com/13547/1/Biochemistry%2C%20Vol.%2030%2C%20No.%203%2C%201991.pdf
Prakash, V. and Timasheff, S. N. (1991) Mechanism of Interaction of Vinca Alkaloids with Tubulin: Catharanthine and Vindoline. Biochemistry, 30. pp. 873-880. ISSN 0006-2960 |
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