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Synthesis of Ziconotide by Solid Phase Method Via Selective Oxidation

Author: CaoBenWen
Tutor: LiZhanXiong;XuHongYan
School: Suzhou University
Course: Textile Chemistry and Dyeing and Finishing Engineering
Keywords: peptide linear peptides ziconotide disulfide bonds Selective Oxidation
CLC: TQ463
Type: Master's thesis
Year: 2011
Downloads: 72
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Abstract


In this dissertation, using the different oxidation reactivity of sulfhydryls with different protective group, two different protected linear peptidesⅠand linear peptidesⅡwere synthesised via solid phase method. Using these two linear peptides as material, the same aimed product was synthesized by selective oxidation via two different synthetic procedures.In the molecule of linear peptidesⅠ, the 8-, 15-, 20- and 25- position sulfhydryls were protected by Trt, and 1- and 16- position sulfhydryls were protected by Acm. But in linear peptidesⅡ, the 1-, 16-, 8- and 20- position sulfhydryls were protected by Trt, 15- and 20- position sulfhydryls were protected by Acm. After other side chain protecting groups was removed using TFA, the linear peptidesⅠandⅡwere purified by HPLCwith the purity to be up to 90%.Using linear peptidesⅠand linear peptidesⅡas materials respectively, the Trt protect groups were removed by air oxidation to formatted two disulfide bonds and to give two kind of partial cyclization peptides. The purity of partial cyclization peptides were up to 90% after purified by HPLC. Then, the third disulfide bond was formed between the sulfhydryls protected by Acm with iodine oxidation. As a result, two kinds of cyclization peptides (A) and (B) were obtained, and the purity was identified to be up to 90%. These two cyclization peptides (A) and (B) were determined to be the same compounds of ziconotide by HPLC and MS technique, and the aimed products were characterized by FT-IR and ~1HNMR.The effect of the oxidant and reduction system used in the removal of Trt groups on the reaction was discussed. The oxidation reaction condition, such as reaction time, slovent, the the amount of iodine, and so on, were investigated in iodine oxidation process. The optimum reaction conditions were determined to be as follows: using air as oxidants, cys as reducing agent in the removal of Trt groups, and 25% methanol aqe. as solvent, the amount of iodine was 8 e.q , the reaction time was 2h.

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