Abstract: α-conotoxins, extracted from conus venoms, are a family of active peptides. The most characteristic and predominant features of these small peptides are fewer disulfide bonds, simpler structure, and higher toxicity compared with other families of conotoxins that they have antagonists of nicotinic acetylcholine and target to subtypes of nicotinic acetylcholine receptor at neuromuscular junction, α-conotoxins make themselves effective tools for identifying the subtypes of nicotinic acetylcholine receptors and the best lead compounds for reconstructing structures of conotoxins. Electronic structures of eight typicalα-conotoxins were calculated by quantum chemical semi-empirical AM1 method of HyperChem soft package. Results of studies on electronic structures and structure-relationship indicated that resemblance of global structures make them target to the same receptors, and difference of electronic structures led by difference of local structures make them target to differential subtypes of receptors. Based on the results, seven analogs of conotoxin GI were designed and calculated by quantum chemical method. Features of GI and analogs on the aspect of spatial structure and electronic structure were compared.

Key words: α-conotoxins, Nicotinic acetylcholine receptor, Electronic structure, Structure-activity relationship, Molecular design