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Year 2018, Volume: 5 Issue: 2, 719 - 726, 01.01.2018
https://doi.org/10.18596/jotcsa.408517

Abstract

References

  • 1. Debin, JA, Maggio JE, Strichartz, GR. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am. J. Physiol. Cell Physiol. 1993; 264(2):C361-C369.
  • 2. Deshane J, Garner CC, Sontheimer H. Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2. J. Biol. Chem. 2003; 278(6):4135-4144.
  • 3. Veiseh M, Gabikian P, Bahrami SB, Veiseh O, Zhang M, Hackman RC, Ravanpay AC, Stroud MR, Kusuma Y, Hansen SJ, Kwok D, Munoz NM, Sze RW, Grady WM, Greenberg NM, Ellenbogen RG, Olson JM. Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci. Cancer Res. 2007; 67(14):6882-6888.
  • 4. Yang C, Hou VW, Girard EJ, Nelson LY, Siebel EJ. Target-to-Background Enhancement in Multispectral Endoscopy with Background Autofluorescence Mitigation for Quantitative Molecular Imaging. J. Biomed. Opt. 2014; 19(7):076014.
  • 5. Kesavan K, Ratliff J, Johnson EW, Dahlberg W, Asara JM, Misra P, Frangioni JV, Jacoby DB. Annexin A2 Is a Molecular Target for TM601, a 51 Peptide with Tumor-Targeting and Anti-Angiogenic Effects. J. Biol. Chem. 2010; 285(7):4366-4374.
  • 6. Akcan M, Stroud MR, Hansen SJ, Clark RJ, Daly NL, Craik DJ, Olson JM. Chemical Re-engineering of Chlorotoxin Improves Bioconjugation Properties for Tumor Imaging and Targeted Therapy. J. Med. Chem. 2011; 54(3):782-787.
  • 7. Elvheim, I. S. Design, Synthesis and Structural Studies of Relaxin Receptor Modulators. 2011; Master's thesis, Universitetet i Tromsø.
  • 8. Behrendt R, White P, Offer J. Advances in Fmoc Solid-Phase Peptide Synthesis. J. Pept. Sci. 2016; 22(1):4-27.
  • 9. Dawson P, Muir T, Clark-Lewis I, Kent S. Synthesis of Proteins by Native Chemical Ligation. Science 1994; 266(5186):776-779.
  • 10. Blanco-Canosa JB, Dawson PE. An Efficient Fmoc-SPPS Approach for the Generation of Thioester Peptide Precursors for Use in Native Chemical Ligation. Angew. Chem. Int. Ed. 2008; 120(36):6957-6961.
  • 11. Amblard M, Fehrentz J, Martinez J, Subra G. Methods and Protocols of Modern Solid Phase Peptide Synthesis. Mol. Biotechnol. 2006; 33:239-254.

Synthesis of Chlorotoxin by Native Chemical Ligation

Year 2018, Volume: 5 Issue: 2, 719 - 726, 01.01.2018
https://doi.org/10.18596/jotcsa.408517

Abstract



Chlorotoxin (CLTX) is a neurotoxin found in the venom of
the Israeli scorpion, Leirius
quinquestriatus. It contains 36-amino acids with four disulfide bonds and inhibits
low-conductance chloride channels. CLTX also binds to matrix
metalloproteinase-2 (MMP-2) selectively. The synthesis of chlorotoxin using
solid phase peptide synthesis (SPPS) is very difficult and has a very low yield
(<1%) due to high number of amino acid sequence. In this work, to improve the
efficiency of the synthesis, native chemical ligation was applied. In this strategy,
chlorotoxin sequence was split into two parts having 15 and 21 amino acids. 21-mer
peptide was synthesized in its native form based on
9-fluorenylmethyloxycarbonyl (Fmoc) chemistry. 15-mer peptide was synthesized
having o-aminoanilide linker on C-terminal. These parts were coupled by native
chemical ligation to produce chlorotoxin. 

References

  • 1. Debin, JA, Maggio JE, Strichartz, GR. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am. J. Physiol. Cell Physiol. 1993; 264(2):C361-C369.
  • 2. Deshane J, Garner CC, Sontheimer H. Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2. J. Biol. Chem. 2003; 278(6):4135-4144.
  • 3. Veiseh M, Gabikian P, Bahrami SB, Veiseh O, Zhang M, Hackman RC, Ravanpay AC, Stroud MR, Kusuma Y, Hansen SJ, Kwok D, Munoz NM, Sze RW, Grady WM, Greenberg NM, Ellenbogen RG, Olson JM. Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci. Cancer Res. 2007; 67(14):6882-6888.
  • 4. Yang C, Hou VW, Girard EJ, Nelson LY, Siebel EJ. Target-to-Background Enhancement in Multispectral Endoscopy with Background Autofluorescence Mitigation for Quantitative Molecular Imaging. J. Biomed. Opt. 2014; 19(7):076014.
  • 5. Kesavan K, Ratliff J, Johnson EW, Dahlberg W, Asara JM, Misra P, Frangioni JV, Jacoby DB. Annexin A2 Is a Molecular Target for TM601, a 51 Peptide with Tumor-Targeting and Anti-Angiogenic Effects. J. Biol. Chem. 2010; 285(7):4366-4374.
  • 6. Akcan M, Stroud MR, Hansen SJ, Clark RJ, Daly NL, Craik DJ, Olson JM. Chemical Re-engineering of Chlorotoxin Improves Bioconjugation Properties for Tumor Imaging and Targeted Therapy. J. Med. Chem. 2011; 54(3):782-787.
  • 7. Elvheim, I. S. Design, Synthesis and Structural Studies of Relaxin Receptor Modulators. 2011; Master's thesis, Universitetet i Tromsø.
  • 8. Behrendt R, White P, Offer J. Advances in Fmoc Solid-Phase Peptide Synthesis. J. Pept. Sci. 2016; 22(1):4-27.
  • 9. Dawson P, Muir T, Clark-Lewis I, Kent S. Synthesis of Proteins by Native Chemical Ligation. Science 1994; 266(5186):776-779.
  • 10. Blanco-Canosa JB, Dawson PE. An Efficient Fmoc-SPPS Approach for the Generation of Thioester Peptide Precursors for Use in Native Chemical Ligation. Angew. Chem. Int. Ed. 2008; 120(36):6957-6961.
  • 11. Amblard M, Fehrentz J, Martinez J, Subra G. Methods and Protocols of Modern Solid Phase Peptide Synthesis. Mol. Biotechnol. 2006; 33:239-254.
There are 11 citations in total.

Details

Primary Language English
Subjects Chemical Engineering
Journal Section Articles
Authors

Ulvi Karaca This is me 0000-0002-8315-0949

Seçkin Kesici This is me 0000-0001-6281-5537

Salih Özçubukçu 0000-0001-5981-1391

Publication Date January 1, 2018
Submission Date March 21, 2018
Acceptance Date April 17, 2018
Published in Issue Year 2018 Volume: 5 Issue: 2

Cite

Vancouver Karaca U, Kesici S, Özçubukçu S. Synthesis of Chlorotoxin by Native Chemical Ligation. JOTCSA. 2018;5(2):719-26.