Here, we report the nAChR subtype-selectivity of exactin and provide evidence for the involvement of loop–I and loop–III in the subtype-selectivity and binding parameters of Ω-neurotoxins. Therefore, delineation of functional determinants that are critical for these charcteristics of Ω-neurotoxins, would be interesting. This can be achieved by site-directed mutational analysis of exactin, This would also help us understand the structure-activity relationship of exactin’s dual function.
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These studies may provide a fundamental basis for the design of highly selective ligands for nAChR subtypes. In the long run, these findings may facilitate in designing a chimera of α-neurotoxin (with high nAChR affinity) and Ω-neurotoxin (with determinants conferring subtype selectivity). Such a ligand chimera would address many questions associated with the normal physiology of nAChR subtypes and also could be used as therapeutic lead for various nAChR associated diseases.
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Appendix
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Figure A.1 Vector map and the MCS of pET-22b. (A) Vector diagram of pET- 32a with all the essential features of the vector. (B) The region corresponding to the multiple cloning site (MCS).
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Table A.3 RP-HPLC chromatograms of the prification of refolded, 12 Oh9-1 alanine mutants and their ESI mass spectrum. They are labled and arranged in side by side fashion for a comparitive view from A to X in the order of loop-I, loop-II and loop-III mutants.
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