片段法合成抗骨质疏松多肽药物特立帕肽

Synthesis of Anti-osteoporotic Peptide Drug Teriparatide by Fragment Condensation Method

将特立帕肽序列中的34个氨基酸分成4个片段:1-11、12-16、17-24和25-34;以Wang Resin(王树脂)为固相载体制得25-34肽树脂;以CTC Resin(2-氯三苯甲基氯树脂)为固相载体制得1-11、12-16和17-24等3个片段的全保护肽,然后将3个片段的全保护肽按照肽序依次缩合到25-34的肽树脂上,经三氟乙酸切割并脱除侧链保护基得特立帕肽粗品,再经液相色谱纯化得特立帕肽,纯度大于99%,总收率达33%,其结构经MS(ESI)确证。

Thirty four amino acids in the sequence of teriparatide were divided into four fragments： 1-11,12-16,17-24 and 25-34. The 25-34 fragment peptide resin was prepared with Wang Resin as solid carrier. The first three protected fragments were obtained by CTC Resin as the solid carrier,and then condensed into 25-34 peptide resin followed by peptide sequence. The crude Teriparatide was synthesized by cleavage and removal of the side chain protecting group using trifluoroacetic acid,purification by RP-HPLC with overall yield of 33% and HPLC purity over 99%. The structure was confirmed by MS（ ESI）.