Roles of Individual Disulfide Bridges in the Conformation and Activity of μ-Conotoxin GIIIA, a Peptide Blocker of Muscle Sodium Channels



Seven analogs of μ-conotoxin GIIIA (μ-GIIIA), a specific blocker of muscle sodium channels, were synthesized by replacing stepwise the three cystine residues with Ala. The circular dichroism spectra of the analogs suggested that the deletion of disulfide bonds gradually randamized a conformation. The inhibitory effects on the twitch contractions of the rat diaphragm showed that the deletion of one disulfide bond reduced the potency to less than 1 % of control. Monocyclic analogs and a linear analog were almost inactive. Therefore, all three disulfide bridges are essential for stabilizing the specific conformation of μ-GIIIA to show biological activity.


μ-Conotoxin GIIIA Sodium channel Disulfide bond Structure–activity relation 







Circular dichroism


Fast atom bombardment-mass spectrometry


μ-Conotoxin GIIIA


High performance liquid chromatography






Nuclear magnetic resonance



The authors wish to express their appreciation to Dr. Hideyoshi Higashi of Mitsubishi Kagaku Institute of Life Sciences for providing measurements of FAB-MS and also to Prof. Scott Pugh of Fukuoka Women’s University for correction of English usage of this manuscript.

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical Standard

All institutional and national guidelines for the care and use of laboratory animals were followed. This article does not include any studies using human subjects.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Environmental ScienceFukuoka Women’s UniversityFukuokaJapan
  2. 2.Faculty of Health Science TechnologyBunkyo Gakuin UniversitySaitamaJapan

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