Abstract:Conotoxins (conopeptides, CTxs) are praised as “Marine drug mine”, which target various ion channels and receptors of animal kingdom. Among them, α*-conotoxins (α*-CTxs) are effective antagonists of subtypes of nicotinic acetylcholine receptors (nAChRs) with high selectivity. Different combinations of nAChR subunits form subtypes of nAChRs that are important in normal physiology, and in a wide range of disease states. Understanding of these functions may be greatly facilitated by discovery and characterization of selective α*-CTxs probes. Mechanistic insight into the structure, function and receptor interaction of α*-CTxs may serve as a platform for the development of selective medications for many nAChRs-related diseases, including neuralgia, chemotherapeutics, addiction, Alzheimer’s disease (AD), myasthenia gravis, schizophrenia, epilepsy, breast and lung carcinoma, experimental autoimmune encephalomyelitis (EAE) etc. Previously, we have identified five novel α*-conotoxins from Hainan cone snails targeting different nAChR subtypes, of which synthesis, 3-dimensional structure, target and interaction with receptors were investigated systematically. This review will focus on their characteristics and application prospects.