Abstract
INTERNATIONAL JOURNAL OF ENGINEERING, SCIENCE AND - Volume 7, Issue 4 (3) , April 2018 (Special Issue FBSA)
Pages: 94-104
Unusual Binding Properties of B-ring Analogs of Colchicine Controlled by B-ring Side Chain
Lalita Das ? Bhabatarak Bhattacharyya ??
Category:Engineering, Science and Mathematics
Abstract:
In this study, we have shown that quantum yield, fluorescence property, activation energy and pH dependence of aminocolchicinoids binding with tubulin are controlled at different points of B-ring and its side chain at C-7 position. The substituent at the C-7 position of the B-ring seems to dictate the relative quantum yield of the colchicinoid-tubulin complexes. We synthesized two compounds, NHCSCH3-DAAC and in NHCH2COCH3-DAAC. Mechanism of induction of fluorescence was elaborately discussed with these compounds. From the X-ray structure of tubulin-damacolchicine complex, it is known that A- and C-ring of colchicine bind at ?-tubulin whereas C-7 side chain of B-ring interacts with ?-tubulin. Here we have shown that although the colchicinoid molecules bind essentially at ?-tubulin, ?-C-terminus has no role on colchicinoids binding with tubulin. But binding is significantly less for both C-termini depleted tubulin (?s?s), which can be explained by a inter-subunit communication through the 'tail-body' interaction. Moreover, we observed that the activation energy of NHCSCH3-DAAC and NHCH2COCH3-DAAC are low and independent of pH. Under identical conditions, the activation energy of N(Me)COCF3-DAAC is high, like colchicine and shows pH dependency. The addition of acetyl group in colchicine causes dramatic decrease in off-rate constant from DAAC. These results indicate that the oxygen atom plays a very significant role which is still unknown to us. It may also possible that the amino and carbonyl groups of B-ring side chain are involved in making important contacts with protein in complex form.
Keywords: Tubulin, Colchicine, B-ring analogs, pH effect, Quantum Yield