A C-terminal fragment of chlorotoxin retains bioactivity and inhibits cell migration

Dastpeyman, Mohadeseh, Giacomin, Paul, Wilson, David, Nolan, Matthew J., Bansal, Paramjit S., and Daly, Norelle L. (2019) A C-terminal fragment of chlorotoxin retains bioactivity and inhibits cell migration. Frontiers in Pharmacology, 10. 250.

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Chlorotoxin was originally isolated from the venom of the Israeli scorpion Leiurus quinquestriatus, and has potential as a tumor imaging agent based on its selective binding to tumor cells. Several targets have been suggested for chlorotoxin including voltage-gated chloride channels, and it has been shown to have anti-angiogenic activity and inhibit cell migration. The structure of chlorotoxin is stabilized by four disulfide bonds and contains β-sheet and helical structure. Interestingly, the reduced form has previously been shown to inhibit cell migration to the same extent as the wild type, but structural analysis indicates that the reduced form of the peptide does not maintain the native secondary structure and appears unstructured in solution. This lack of structure suggests that a short stretch of amino acids might be responsible for the bioactivity. To explore this hypothesis, we have synthesized fragments of chlorotoxin without disulfide bonds. As expected for such small peptides, NMR analysis indicated that the peptides were unstructured in solution. However, the peptide corresponding to the eight C-terminal residues inhibited cell migration, in contrast to the other fragments. Our results suggest that the C-terminal region plays a critical role in the bioactivity of chlorotoxin.

Item ID: 60630
Item Type: Article (Research - C1)
ISSN: 1663-9812
Keywords: chlorotoxin, tumor-imaging agent, metastasis, migration, invasion, disulfide-rich peptide
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Copyright Information: © 2019 Dastpeyman, Giacomin, Wilson, Nolan, Bansal and Daly. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
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A version of this publication was included as Chapter 2 of the following PhD thesis: Dastpeyman, Mohadeseh (2019) Structure-function relationships of disulfide-rich peptides. PhD thesis, James Cook University, which is available Open Access in ResearchOnline@JCU. Please see the Related URLs for access.

Funders: Future Fellowship (FF), Advance Queensland Mid-Career Fellowship, Australian Research Council (ARC)
Projects and Grants: FF 110100226, ARC LE120100015, ARC LE160100218
Date Deposited: 28 Jan 2020 21:34
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320506 Medical biochemistry - proteins and peptides (incl. medical proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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