Chlorotoxin (CLTX)

Chlorotoxin (ClTX) is a peptide toxin from the venom of the scorpion "leiurus quinquestriatus" (Deathstalker) and it blocks small‐conductance chloride channels.

Source

It’s purified from crude leiurus, which belongs to scorpion toxin super family (Debin 1993).

Chemistry

Chlorotoxin is a small toxin and at PH= 7 is highly cationic. Chlorotoxin is a peptide consists of 30‐35 amino acids and 4 disulfide bonds. 8 Cystein amino acids among its total number of amino acids present in the structure of this peptide, are connected with the 4‐disulfide bonds in their configuration and in the following order (Lippens G 1995):Cys2‐‐‐‐‐‐cys19Cys5‐‐‐‐‐‐cys28Cys16‐‐‐‐‐cys33Cys20‐‐‐‐‐cys35

Target

Chlorotoxin is a chloride channel ligand and it blocks small‐conductance chloride channels. Each chloride channel can be closed by only one ligand molecule (Debin 1993).

Toxicity

Chlorotoxin causes the prey, which has been targeted by the venom become immobilized. Depending on level of the injected venom the duration of paralysis can vary (Debin 1993).

Therapeutic use

The blocking effect of chlorotoxin on tumor cells of neuroectodermal origin can target these kinds of cells while this toxin does not show any harmful impact on healthy cells beside the tumor cells. CLTX has the ability to interact with chloride channels in membrane protein in glioma cells, so this prevents transmembrane chloride fluxes but this interaction does not happen for the neurons and normal glial cells. This suggests a great hope for treating cancer. The mechanism behind these opposite behaviors is under study (Lyons 2002).

References:

* John A. Debin, John E. Maggio,Gary R (1993). "STRICHARTZPurification and characterization of chlorotoxin, a chloride channel ligand fromthe venom of the scorpion".Cell Physiology, Vol 264, Issue 2 C361-C369. PMID: 8383429 [http://www.ncbi.nlm.nih.gov/pubmed/8383429?dopt=Abstract]
* Susan A. Lyons, Jeffrey O'Neal, Harald Sontheimer (2002). "Clorotoxin, a Scorpion‐Derived Peptide, Specifically Binds to Gliomas andTumors of Neuroectodermal Origin". Glia, Vol 39, Issue 2, Pages 162 - 173. [http://www3.interscience.wiley.com/journal/94515876/abstract]
* Lippens G, Najib J, Wodak SJ, Tartar A (1995). "NMR sequential assignments and solution structure of chlorotoxin, a smallscorpion toxin that blocks chloride channel". Biochemistry Vol 34, Issue 1, Pages 13-21. PMID: 7819188 [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=7819188]