发明授权
- 专利标题: Insulinotropic peptide synthesis using solid and solution phase combination techniques
- 专利标题(中): 使用固相和溶液相组合技术的胰岛素肽合成
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申请号: US12316309申请日: 2008-12-11
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公开(公告)号: US08227571B2公开(公告)日: 2012-07-24
- 发明人: Lin Chen , Yeun-Kwei Han , Christopher R. Roberts
- 申请人: Lin Chen , Yeun-Kwei Han , Christopher R. Roberts
- 申请人地址: US CA South San Francisco
- 专利权人: Roche Palo Alto LLC
- 当前专利权人: Roche Palo Alto LLC
- 当前专利权人地址: US CA South San Francisco
- 代理商 Brian L. Buckwalter
- 主分类号: C07K14/00
- IPC分类号: C07K14/00
摘要:
The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase (“hybrid”) approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to the third fragment which is then coupled to the second fragment and then the first fragment in solution. Alternatively, a different second fragment is coupled to the first fragment in the solid phase. Then, solution phase chemistry is then used to add additional amino acid material to a different third fragment. Subsequently, this different third fragment is coupled to the coupled first and different second fragment in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to the other fragments. The present invention is very useful for forming insulinotropic peptides such as GLP-1(7-36) and its natural and non-natural counterparts.
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