B ring regulation of colchicine binding kinetics and fluorescence

Bhattacharyya, B. ; Howard, Rosilyn ; Maity, S. N. ; Brossi, A. ; Sharma, P. N. ; Wolff, J. (1986) B ring regulation of colchicine binding kinetics and fluorescence Proceedings of the National Academy of Sciences of the United States of America, 83 . pp. 2052-2055. ISSN 0027-8424

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Official URL: http://www.pnas.org/content/83/7/2052.abstract?sid...


Several properties of the colchicine-tubulin interaction such as association rate, reversibility, and the promotion of drug fluorescence have been related to the B ring of colchicine. The B ring itself retards the binding rate, and substitution at C-7 leads to further binding rate decreases that appear to be related to both substituent bulk and the presence of a N-acyl group. Thus, the decreasing order of binding rates is 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone > deacetamidocolchicine > deacetylcolchicine ≥ colcemid > colchicine > N-benzoyldeacetylcolchicine, etc. The apparent irreversibility of the binding seems more closely related to the presence of an N-acyl group rather than the bulk of the substituent at C-7. Substitution at C-7 also affects the tropolone fluorophore. Thus, amines (deacetylcholchicine, colcemid, or N-methylcolcemid) fluoresce poorly in the presence of tubulin, whereas substitution of the amino group with an acyl group enhances fluorescence. The presence of an N-acyl group at C-7 is essential for enhanced fluorescence. We conclude that, in addition to A- and the C-ring portion of the molecule, the B ring of colchicine is a third determinant recognized by the binding site on tubulin.

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ID Code:26240
Deposited On:06 Dec 2010 12:52
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