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

作　　者：周建华 陆丹 朱永明[1] ZHOU Jian-hua;LU Dan;ZHU Yong-ming(School of Pharmaceutical Sciences,Medical College,Sooehow University,Suzhou 215123,China;Suzhou Thery Pharmaceutical Ine,Suzhou 215123,China)

机构地区：[1]苏州大学医学部药学院,江苏苏州215123 [2]苏州特瑞药业有限公司,江苏苏州215151

出　　处：《合成化学》2018年第8期596-601,共6页Chinese Journal of Synthetic Chemistry

摘　　要：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）.

关 键 词：特立帕肽 片段缩合 固相合成 多肽药物 药物合成 抗骨质疏松 

分 类 号：R914.5[医药卫生—药物化学] O629.7[医药卫生—药学]