发明名称 |
METHOD FOR SOLID PHASE SYNTHESIS OF LIRAGLUTIDE |
摘要 |
Provided is a method for solid phase synthesis of liraglutide, comprising the following steps: A), Fmoc-Gly-resin being obtained by coupling resin solid phase carrier with glycine with N-end protected by Fmoc(Fmoc-Gly-OH) in the presence of activator system; B) according to the peptide sequence of the main chain of liraglutide, successively coupling with amino acids with N-ends protected by Fmoc and protected side chains by the method for solid phase synthesis, wherein lysine employs Fmoc-Lys(Alloc)-OH; C) removing the protective group, Alloc, from the side chain of lysine; D) couplilng the side chain of lysine with Palmitoyl-Glu-Offiu by the method for solid phase synthesis; E) cleavage, removing protection groups and resin to obtain crude liraglutide; F) purifying and lyophilizing to obtain liraglutide. |
申请公布号 |
US2014350219(A1) |
申请公布日期 |
2014.11.27 |
申请号 |
US201214344660 |
申请日期 |
2012.08.30 |
申请人 |
Pan Junfeng;Liu Jian;Ma Yaping;Yuan Jiancheng |
发明人 |
Pan Junfeng;Liu Jian;Ma Yaping;Yuan Jiancheng |
分类号 |
C07K1/04;C07K1/14 |
主分类号 |
C07K1/04 |
代理机构 |
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代理人 |
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主权项 |
1. A method for solid phase synthesis of liraglutide, which is characterized in that the method comprises the following steps:
A) in the presence of an activating agent system, Fmoc-Gly-resin is obtained by coupling N-terminal Fmoc-protected glycine (Fmoc-Gly-OH) to a resin solid-phase support; B) by solid-phase synthesis, amino acids with N-terminal Fmoc protection and side chain protection are sequentially coupled based on the sequence of peptide backbone of liraglutide, wherein Fmoc-Lys(Alloc)-OH is employed for lysine; C) the protective group Alloc for side chain of lysine is removed; D) by solid phase synthesis, palmitoyl-Glu-OtBu is coupled to the side chain of lysine; E) crude liraglutide is obtained by cleavage, and removal of the protective groups and the resin; F) liraglutide is finally obtained by purification and lyophilizing. |
地址 |
Shenzhen CN |