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1. 发明申请

WO2005063791B1 PROCESS FOR PEPTIDE SYNTHESIS USING A REDUCED AMOUNT OF DEPROTECTION AGENT 审中-公开
标题翻译：使用减少剂量的保护剂进行肽合成的方法
公开(公告)号：WO2005063791B1
公开(公告)日：2005-11-10
申请号：PCT/EP2004014599
申请日：2004-12-22
申请人： HOFFMANN LA ROCHE , GUINN MARTIN R , HODGES LEWIS M , JOHNSTON DAVID A , MOORLAG HENDRICK , SCHWINDT MARK A
发明人： GUINN MARTIN R , HODGES LEWIS M , JOHNSTON DAVID A , MOORLAG HENDRICK , SCHWINDT MARK A
IPC分类号： C07K1/02 , C07K1/04
CPC分类号： C07K1/04 , C07K1/026 , Y02P20/55
摘要： The invention provides methods of synthesizing peptides, involving the steps of providing a composition including a peptide fragment, wherein the peptide fragment has at least one amino acid residue and includes a base-sensitive, N-terminal protecting group; removing the base-sensitive, N-terminal protecting group from the peptide fragment using a deprotection reagent that includes a base, whereby an N-terminal functionality on the peptide fragment is deprotected; removing the base from the composition to provide a residual base content of more than 100 ppm; causing a reactive peptide fragment having a reactive C-terminus and a base-sensitive N-terminal protecting group to react with the deprotected N-terminal functionality of the peptide fragment under conditions such that the reactive peptide fragment is added to the peptide fragment; and optionally repeating the deprotection and coupling steps until a desired peptide is obtained. Also provided are methods of synthesizing peptides, wherein base is removed from the composition to a point where the composition would provide a positive chloranil test. Also provided are methods of synthesizing peptides, wherein coupling is performed in basic reaction mixtures.
摘要翻译：本发明提供了合成肽的方法，包括提供包括肽片段的组合物的步骤，其中肽片段具有至少一个氨基酸残基并且包括碱敏感的N-末端保护基; 使用包含碱的去保护试剂从肽片段中除去碱敏感的N-末端保护基，由此将肽片段上的N-末端官能团去保护; 从组合物中除去碱以提供大于100ppm的残留碱含量; 使得具有反应性C末端和碱敏感性N末端保护基团的反应性肽片段与肽片段的去保护的N末端官能团反应，使得将反应性肽片段加入到肽片段中; 并任选地重复脱保护和偶联步骤，直至获得所需的肽。还提供了合成肽的方法，其中将碱从组合物中除去至组合物将提供正氯醌测试的程度。还提供了合成肽的方法，其中在碱性反应混合物中进行偶联。

2. 发明申请

WO2005063791A2 PROCESS AND SYSTEMS FOR PEPTIDE SYNTHESIS 审中-公开
标题翻译：肽合成的方法和系统
公开(公告)号：WO2005063791A2
公开(公告)日：2005-07-14
申请号：PCT/EP2004014599
申请日：2004-12-22
申请人： HOFFMANN LA ROCHE , GUINN MARTIN R , HODGES LEWIS M , JOHNSTON DAVID A , MOORLAG HENDRICK , SCHWINDT MARK A
发明人： GUINN MARTIN R , HODGES LEWIS M , JOHNSTON DAVID A , MOORLAG HENDRICK , SCHWINDT MARK A
IPC分类号： C07K1/02 , C07K1/04 , C07K1/00
CPC分类号： C07K1/04 , C07K1/026 , Y02P20/55
摘要： The invention provides methods of synthesizing peptides, involving the steps of providing a composition including a peptide fragment, wherein the peptide fragment has at least one amino acid residue and includes a base-sensitive, N-terminal protecting group; removing the base-sensitive, N-terminal protecting group from the peptide fragment using a deprotection reagent that includes a base, whereby an N-terminal functionality on the peptide fragment is deprotected; removing the base from the composition to provide a residual base content of more than 100 ppm; causing a reactive peptide fragment having a reactive C-terminus and a base-sensitive N-terminal protecting group to react with the deprotected N-terminal functionality of the peptide fragment under conditions such that the reactive peptide fragment is added to the peptide fragment; and optionally repeating the deprotection and coupling steps until a desired peptide is obtained. Also provided are methods of synthesizing peptides, wherein base is removed from the composition to a point where the composition would provide a positive chloranil test. Also provided are methods of synthesizing peptides, wherein coupling is performed in basic reaction mixtures.
摘要翻译：本发明提供了合成肽的方法，包括提供包括肽片段的组合物的步骤，其中肽片段具有至少一个氨基酸残基并且包括碱敏感的N-末端保护基; 使用包含碱的去保护试剂从肽片段中除去碱敏感的N-末端保护基，由此将肽片段上的N-末端官能团去保护; 从组合物中除去碱以提供大于100ppm的残留碱含量; 使得具有反应性C末端和碱敏感性N末端保护基团的反应性肽片段与肽片段的去保护的N末端官能团反应，使得将反应性肽片段加入到肽片段中; 并任选地重复脱保护和偶联步骤，直至获得所需的肽。还提供了合成肽的方法，其中将碱从组合物中除去至组合物将提供正氯醌测试的程度。还提供了合成肽的方法，其中在碱性反应混合物中进行偶联。

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