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    Chlorotoxins、氯毒素
    • Chlorotoxins、氯毒素的介紹

      Definition

      Chlorotoxin is a 36-amino acid peptide found in the venom of the death-stalker scorpion (Leiurus quinquestriatus) which blocks small-conductance chloride channels1.

      Discovery

      Chlorotoxin was first purified from scorpion venum in 19931. 

      Classification

      Chlorotoxin belongs to the scorpion toxin superfamily1. 

      Structural Characteristics

      Chlorotoxin is a small positive charged peptide consisting of 30-35 amino acids and 4 disulfide bonds2. Eight cysteine amino acids among its total number of amino acids present in the structure of this peptide are connected with four disulfide bonds2. 

      Mode of action

      Chlorotoxin specifically binds to matrix-metalloproteinase receptor on glioma cells and inhibits it3. It also acts as a ligand for chloride channels and blocks them4. 

      Functions

      As chlorotoxin binds preferentially to glioma cells compared with non-neoplastic cells or normal brain it has has been used to develop new methods for the treatment and diagnosis of several types of cancer5.  Chlorotoxin: Cy5.5 bioconjugate has been recently used to demarcate cancer cells from the surrounding normal cells. This gives surgeons a better chance of removing all of the cancerous cells without injuring the surrounding healthy tissue6. 

      References          

      1. DeBin JA, Maggio JE, Strichartz GR (1993). Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am. J. Physiol., 264 (2 Pt 1), C3619.

      2. Lippens G, Najib J, Wodak SJ, Tartar A (1995). NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels. Biochemistry, 34 (1): 1321.

      3. Deshane J, Garner CC, Sontheimer H (2003). Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J. Biol. Chem., 278 (6), 413544.

      4. DeBin JA, Strichartz GR (1991). Chloride channel inhibition by the venom of the scorpion Leiurus quinquestriatue. Toxicon, 29 (11), 14038.

      5. Lyons SA, O'Neal J, Sontheimer H (2002). Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia 39 (2), 16273.

      6. Veiseh M, Gabikian P, Bahrami SB, et al (2007). Tumor paint: a chlorotoxin: Cy5.5 bioconjugate for intraoperative visualization of cancer foci. Cancer Res., 67 (14), 68828.

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