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Updated: Apr 20, 2026

Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
The role of disulfide bonds in structure and activity of chlorotoxin
Paola G Ojeda1, Lai Y Chan, Aaron G Poth
1Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, QLD, Australia.
Background:
Chlorotoxin is a small scorpion peptide that inhibits glioma cell migration. We investigated the importance of a major component of chlorotoxin's chemical structure - four disulfide bonds - to its tertiary structure and biological function.
Results:
Five disulfide bond analogs of chlorotoxin were synthesized, with l-α-aminobutyric acid residues replacing each or all of the disulfide bonds. Chemical oxidation and circular dichroism experiments revealed that Cys III-VII and Cys V-VIII were essential for native structure formation. Cys I-IV and Cys II-VI were important for stability of enzymatic proteolysis but not for the inhibition of human umbilical vein endothelial cell migration.
Conclusion:
The disulfide bonds of chlorotoxin are important for its structure and stability and have a minor role in its activity against cell migration.
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