Abstract
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.
Financial & competing interests disclosure
The studies described herein were supported by grant from the National Health and Medical Research Council (NHMRC; APP1010552). D Craik is an NHMRC Professorial Fellow (APP1026501) and P Ojeda acknowledges a PhD scholarship from the Comisión Nacional de Investigación Científica y Tecnológica (CONICYT/BecasChile) from Government of Chile. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.