Entropy driven binding of the alkaloid chelerythrine to polyadenylic acid leads to spontaneous self-assembled structure formation |
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| Affiliation: | 1. Brooke Laboratories, Clinical and Experimental Sciences and the Southampton NIHR Respiratory Biomedical Research Unit, Faculty of Medicine, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK;2. Department of Chemistry, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK;3. Engineering Science, Faculty of Engineering and the Environment, University of Southampton, Southampton, UK;4. Institute for Life Sciences, University of Southampton, Southampton, UK;1. School of Chemical Engineering, UNSW Australia, Sydney 2052, NSW, Australia;2. Department of Chemical Engineering, Institute of Technology Sepuluh Nopember, Surabaya, Indonesia;3. College of Agriculture and Applied Biology, Can Tho University, Viet Nam;4. Children’s Cancer Institute Australia, UNSW Australia, Sydney 2052, NSW, Australia;1. Institute of Chemical Materials, China Academy of Engineering Physics (CAEP), Mianyang 621900, PR China;2. Research Center of Laser Fussion, China Academy of Engineering Physics (CAEP), Mianyang 621900, PR China;3. School of Mechano-Electronic Engineering, Beijing Institute of Technology, Beijing 100081, PR China;1. Tsinghua University, Department of Chemistry, Beijing 100084, China;2. The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, China;3. Shenzhen Anti-Tumor Drug Development Engineering Laboratory, the Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China;4. School of Medicine, Tsinghua University, Beijing 100084, China |
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| Abstract: | The binding thermodynamics and interaction of the putative anticancer alkaloid chelerythrine with polyadenylic acid were investigated by isothermal titration calorimetry, absorption and fluorescence spectroscopy, circular dichroism, differential scanning calorimetry and thermal melting experiments. The equilibrium binding constant was evaluated to be of the order of 107 M−1. Strong positive entropic and favorable enthalpic contributions to the binding were revealed. The binding affinity was enhanced within (10 to 100) mM Na+ concentration. Circular dichroism spectra confirmed that the increase in entropy change was caused by a strong conformational change in the RNA polynucleotide. Absorption and circular dichroism melting studies revealed that chelerythrine binding induced self-assembled duplex structure formation in poly(A) molecules resulting in a cooperative melting profile. This was further confirmed from differential scanning calorimetry data. The intercalation binding of the alkaloid involved strong energy transfer from the polynucleotide bases to the bound alkaloid molecules. The remarkably high entropy driven binding of the alkaloid induced spontaneous self-assembled structure formation in poly(A) and the associated binding affinity is the highest so far reported for a small molecule binding to poly(A). |
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| Keywords: | Chelerythrine RNA binding Calorimetry Structural reorganization |
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