%0 Journal Article %T Optimal Cleavage and Oxidative Folding of ¦Á-Conotoxin TxIB as a Therapeutic Candidate Peptide %A Xiaosa Wu %A Yong Wu %A Furong Zhu %A Qiuyuan Yang %A Qianqian Wu %A Dongting Zhangsun %A Sulan Luo %J Marine Drugs %D 2013 %I MDPI AG %R 10.3390/md11093537 %X Alpha6beta2 nicotinic acetylcholine receptors (nAChRs) are potential therapeutic targets for the treatment of several neuropsychiatric diseases, including addiction and Parkinson¡¯s disease. Alpha-conotoxin (¦Á-CTx) TxIB is a uniquely selective ligand, which blocks ¦Á6/¦Á3¦Â2¦Â3 nAChRs only, but does not block the other subtypes. Therefore, ¦Á-CTx TxIB is a valuable therapeutic candidate peptide. Synthesizing enough ¦Á-CTx TxIB with high yield production is required for conducting wide-range testing of its potential medicinal applications. The current study optimized the cleavage of synthesized ¦Á-CTx TxIB resin-bounded peptide and folding of the cleaved linear peptide. Key parameters influencing cleavage and oxidative folding of ¦Á-CTx TxIB were examined, such as buffer, redox agents, pH, salt, co-solvent and temperature. Twelve conditions were used for cleavage optimization. Fifty-four kinds of one-step oxidative solution were used to assess their effects on each ¦Á-CTx TxIB isomers¡¯ yield. The result indicated that co-solvent choices were particularly important. Completely oxidative folding of globular isomer was achieved when the NH 4HCO 3 or Tris-HCl folding buffer at 4 ¡ãC contained 40% of co-solvent DMSO, and GSH:GSSG (2:1) or GSH only with pH 8~8.7. %K ¦Á-conotoxin TxIB %K oxidative folding %K optimization %K therapeutic peptides %U http://www.mdpi.com/1660-3397/11/9/3537