公开(公告)号：US20060167220A1

公开(公告)日：2006-07-27

申请号：US11321035

申请日：2005-12-28

申请人： Richard Dauer ,  Christina Evanson ,  Paul Friedrich ,  Hafez Hafezzadeh ,  Ramakrishna Nalitham ,  Stephen Schneider ,  Mark Schwindt ,  Roger Snyder ,  Joseph White ,  Gregory Withers

发明人： Richard Dauer ,  Christina Evanson ,  Paul Friedrich ,  Hafez Hafezzadeh ,  Ramakrishna Nalitham ,  Stephen Schneider ,  Mark Schwindt ,  Roger Snyder ,  Joseph White ,  Gregory Withers

IPC分类号： C07K14/00

CPC分类号： C07K14/005 ,  C07K1/145 ,  C07K1/303 ,  C07K14/605 ,  C12N2740/16122

摘要： The formation of inactive, insoluble forms of peptide can be minimized or, alternatively, inactive, insoluble forms of peptide compounds, if present, can be converted into more physiologically active, soluble forms by dissolving peptide samples in aqueous base and then acidifying the aqueous mixture to precipitate the peptide in the presence of at least one of a salt and a co-solvent. Preferably, both a salt and co-solvent are present. By carrying out the precipitation relatively rapidly (at least in a first stage of acidifying in which the pH of the alkaline medium is reduced to a pH in the range of 6 to 7.5, after which acidification to a final desired pH, e.g., 3 to 6, can occur more slowly) at relatively low temperature, the dissolution characteristics of the resultant precipitated peptide are even further improved. The process is robust, consistent, and suitable for commercial scale manufacture of peptides.

摘要翻译： 通过将肽样品溶解在碱性水溶液中，然后使含水混合物酸化，可以使肽的无活性，不溶性形式形成，或者如果存在的话，可以通过将肽化合物的不溶形式（如果存在的话）转化为更具生理活性的可溶形式， 以在盐和共溶剂中的至少一种的存在下沉淀肽。 优选地，存在盐和共溶剂。 通过相对快速地进行沉淀（至少在第一阶段的酸化中，将碱性介质的pH降低至6至7.5范围内的pH，然后酸化至最终所需的pH，例如3至 6，可以更慢地发生），在所得沉淀肽的溶解特性进一步提高。 该方法稳健，一致，适用于商业规模生产肽。

公开(公告)号：US20050165215A1

公开(公告)日：2005-07-28

申请号：US11021647

申请日：2004-12-23

申请人： Roger Bigelow ,  Mark Schwindt ,  Gregory Withers

发明人： Roger Bigelow ,  Mark Schwindt ,  Gregory Withers

IPC分类号： A61K38/00 ,  C07K1/02 ,  C07K1/04 ,  C07K1/06 ,  C07K1/12 ,  C07K14/16

CPC分类号： C07K14/005 ,  A61K38/00 ,  C07K1/02 ,  C07K1/04 ,  C07K1/061 ,  C07K1/12 ,  C12N2740/16122

摘要： The invention provides methods for synthesizing peptides, which include taking an organic solvent having non-resin bound protected peptide and performing a deprotection reaction on the non-resin bound protected peptide. In these methods it is not required that the peptide is dried immediately before providing to the deprotection reaction. Also provided are methods of synthesizing peptides, wherein a protected peptide is formed in a solution phase reaction, dissolved into an organic solvent, and then introduced into a deprotection reaction. Also provided are methods of synthesizing peptides, wherein a non-resin bound protected peptide is concentrated in an organic solvent prior to being subject to a deprotection reaction.

摘要翻译： 本发明提供合成肽的方法，其包括取得具有非树脂结合的保护肽的有机溶剂并对非树脂结合的保护肽进行去保护反应。 在这些方法中，不需要在提供去保护反应之前立即干燥肽。 还提供了合成肽的方法，其中将受保护的肽在溶液相反应中形成，溶解到有机溶剂中，然后引入去保护反应。 还提供了合成肽的方法，其中在进行去保护反应之前，将非树脂结合的保护肽浓缩在有机溶剂中。

公开(公告)号：US20050165217A1

公开(公告)日：2005-07-28

申请号：US11021952

申请日：2004-12-23

申请人： Martin Guinn ,  Lewis Hodges ,  David Johnston ,  Hendrik Moorlag ,  Mark Schwindt

发明人： Martin Guinn ,  Lewis Hodges ,  David Johnston ,  Hendrik Moorlag ,  Mark Schwindt

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，包括提供包含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，从而将肽片段上的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。

公开(公告)号：US20050143568A1

公开(公告)日：2005-06-30

申请号：US11021820

申请日：2004-12-23

申请人： Mark Schwindt

发明人： Mark Schwindt

IPC分类号： C07K1/10 ,  C07K1/14 ,  C07K1/30 ,  C07K1/34 ,  C07K14/16

CPC分类号： C07K1/34 ,  C07K14/005 ,  C12N2740/16122

摘要： The invention provides methods for synthesizing peptides, which include a step of filter decanting. Filter decanting involves removing supernatant from a mixture containing a precipitated peptide. A filter decanting apparatus can be used to remove the supernatant. The invention also provides methods, such as deprotection methods, that can be performed prior to the filter decanting method.

摘要翻译： 本发明提供了合成肽的方法，其包括过滤倾析步骤。 过滤倾析涉及从含有沉淀肽的混合物中除去上清液。 可以使用过滤器倾析装置去除上清液。 本发明还提供可以在过滤器倾析方法之前进行的方法，例如去保护方法。