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Novel «marine» molecules in n-acetylcholine receptors research
Researchers from IBCh RAS Department of Molecular Bases of Neurosignalization and Laboratory of the Chemistry of Marine Natural Products at the G.B Elyakov Pacific Institute of bioorganic chemistry (PIBOC FE RAS) isolated an agonist of human nicotinic receptors from Hermissenda carassicornis nudibranch mollusc. This is the first molecule from marine source that activates alpha7 but not the alpha4beta2 nicotinic receptor (nAChR). The structure and properties of this molecule are described in detail in the article published in the Marine Drugs journal.
Nudibranch mollusc Hermissenda carassicornis, inhabiting Pacific ocean is considered as a model object in neuroresearch because it possesses some features of higher organisms, namely generating a reaction in response to specific stimuli (conditioned reflex) such as moving toward changing light, slowing down movements in waves and migrating toward secure regions during storms.
Fig. 1. Nudibranch mollusc Hermissenda carassicornis.
In 2014 these researchers already reported about new low molecular weight compounds interacting with nicotinic receptors. As a result they described new nAChRs-blocking compounds belonging to diverse groups (polycyclic guanidines, sphyngosine derivatives etc., see Fig. 2).
Fig. 2. Polycyclic guanidines, sphyngosine derivatives.
The research was continued now focusing on the nAChR activators and this year they found 6-bromohypaphorine (6-BHP, see Fig. 3) that binds to neuronal alpha7 nAChRs and activates them. Interestingly, the compound does not activate other abundant neuronal nAChRs composed of different subunits. Nicotinic receptors of alpha7 type are involved in cognitive functions of the brain, regulate cell proliferation and immune response.
Рис. 3. 6-bromohypaphorine.
The information obtained about the structure and properties of 6-BHP might be applied for design of new drugs and research tools.
march 19, 2015