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公开(公告)号：US07317129B2
公开(公告)日：2008-01-08
申请号：US11229926
申请日：2005-09-19
申请人： Ronald T. Raines , Laura L. Kiessling , Bradley L. Nilsson , Yi He , Matthew B. Soellner , Ronald J. Hinklin
发明人： Ronald T. Raines , Laura L. Kiessling , Bradley L. Nilsson , Yi He , Matthew B. Soellner , Ronald J. Hinklin
IPC分类号： C07F5/02
CPC分类号： C07F9/5004 , C07F9/5045 , C07K1/006 , C07K5/06026
摘要： The present invention provides improved methods for synthesis of phosphinothiol reagents, as well as novel protected reagents, for use in formation of amide bonds, and particularly, for peptide ligation. The invention provides phosphine-borane complexes useful as reagents in the formation of amide bonds, particularly for the formation of an amide bond between any two of an amino acid, a peptide, or a protein.
摘要翻译： 本发明提供了用于合成膦硫醇试剂以及用于形成酰胺键的新型受保护试剂的改进方法，特别是用于肽连接。 本发明提供了可用作形成酰胺键的试剂的膦 - 硼烷络合物，特别是用于在任何两个氨基酸，肽或蛋白质之间形成酰胺键。
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公开(公告)号：US06974884B2
公开(公告)日：2005-12-13
申请号：US10456988
申请日：2003-06-06
申请人： Ronald T. Raines , Laura L. Kiessling , Bradley L. Nilsson , Yi He , Matthew B. Soellner , Ronald J. Hinklin
发明人： Ronald T. Raines , Laura L. Kiessling , Bradley L. Nilsson , Yi He , Matthew B. Soellner , Ronald J. Hinklin
IPC分类号： C07K2/00 , C07F5/02 , C07F9/02 , C07F9/50 , C07F19/00 , C07K1/00 , C07K5/06 , C07K5/062 , C07K14/00
CPC分类号： C07F9/5004 , C07F9/5045 , C07K1/006 , C07K5/06026
摘要： The present invention provides improved methods for synthesis of phosphinothiol reagents, as well as novel protected reagents, for use in formation of amide bonds, and particularly for peptide ligation. The invention provides phosphine-borane complexes useful as reagents in the formation of amide bonds, particularly for the formation of an amide bond between any two of an amino acid, a peptide, or a protein.
摘要翻译： 本发明提供了用于合成膦硫醇试剂以及用于形成酰胺键的新型受保护试剂，特别是用于肽连接的改进方法。 本发明提供了可用作形成酰胺键的试剂的膦 - 硼烷络合物，特别是用于在任何两个氨基酸，肽或蛋白质之间形成酰胺键。
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公开(公告)号：US06972320B2
公开(公告)日：2005-12-06
申请号：US10276515
申请日：2001-05-11
IPC分类号： C07K1/06 , C07F9/48 , C07F9/50 , C07K1/08 , C07K1/107 , C07K1/12 , C07K1/13 , C07C231/10 , C07K1/02 , C07K1/04
CPC分类号： C07K1/082 , C07F9/4866 , C07F9/5004 , C07F9/5022 , C07F9/5054 , C07K1/1072 , C07K1/1077
摘要： Methods and reagents for the formation of amide bonds between an activated carboxylic acid derivative and an azide useful in the synthesis of peptides, proteins and derivatized or labeled amino acids, peptide or proteins. The method involves the formation of a phosphinothioester which reacts with an azide resulting in amide formation. The invention provides phosphinothiol reagents which convert activated carboxylic acid derivatives to phosphinothioesters which then react with azides to form an amide bond. The methods and reagents of the invention can be used for stepwise synthesis of peptides on solid supports or for the ligation to two or more amino acids, two or more peptide or two or more protein fragments.
摘要翻译： 用于在合成肽，蛋白质和衍生化或标记的氨基酸，肽或蛋白质中有用的活化的羧酸衍生物和叠氮化物之间形成酰胺键的方法和试剂。 该方法涉及形成与产生酰胺形成的叠氮化物反应的膦硫代酯。 本发明提供了将活化的羧酸衍生物转化为硫代磷酸酯的次硫基硫醇试剂，然后与叠氮化物反应形成酰胺键。 本发明的方法和试剂可用于在固体支持物上逐步合成肽或用于连接至两个或更多个氨基酸，两个或更多个肽或两个或更多个蛋白质片段。
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4.发明授权公开(公告)号：US07807140B2
公开(公告)日：2010-10-05
申请号：US11743740
申请日：2007-05-03
IPC分类号： A61B5/055
CPC分类号： A61K49/128
摘要： Polymeric chelating agents and metal chelates, particularly those of lanthanide metals and more specifically those of Gd(III), useful as contrast agents in magnetic resonance imaging (MRI) for therapeutic and diagnostic applications as well as clinical and biomedical research applications. The polymeric chelates are generated using ring-opening metathesis polymerization (ROMP). Polymers can have multiple sites for functionalization allowing for the synthesis of multimodal and targeted contrast agents. Hydroxypyridonate (HOPO)-based chelating moieties are integrated into a ROMP-derived polymer. More specifically, the HOPO-based chelating moiety is integrated into a benzonorbornadiene unit that constitutes the backbone of the polymer. The ROMP-derived polymer chelators can comprise multiple metal ions, particularly Gd(III) ions, in polymers of varying lengths to provide a series of agents with controlled relaxivites. Polymer chelates include those that are water-soluble.
摘要翻译： 聚合螯合剂和金属螯合物，特别是镧系元素金属螯合剂，更具体地，可用作Gd（III）的螯合剂，用作治疗和诊断应用以及临床和生物医学研究应用的磁共振成像（MRI）中的造影剂。 使用开环易位聚合（ROMP）产生聚合物螯合物。 聚合物可以具有多个用于官能化的位点，允许合成多峰和靶向造影剂。 将羟基吡啶酮（HOPO）基螯合部分整合到ROMP衍生的聚合物中。 更具体地，基于HOPO的螯合部分整合成构成聚合物主链的苯并降二烯单元。 ROMP衍生的聚合物螯合剂可以在不同长度的聚合物中包含多种金属离子，特别是Gd（III）离子，以提供具有受控弛豫物质的一系列试剂。 聚合物螯合物包括那些水溶性螯合物。
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公开(公告)号：US08460684B2
公开(公告)日：2013-06-11
申请号：US11084068
申请日：2005-03-18
IPC分类号： A61F2/00
摘要： A class of anionic oligomers and polymers that function for inhibition of nucleases, particularly RNase. Specific inhibitors include mixtures of oligomers of vinyl sulfate. Methods for inhibition or inactivation of one or more nucleases in vitro which comprises the step of contacting the one or more nucleases in a biological medium with one or more of the anionic oligomeric or polymeric inhibitors of this invention. Kits for carrying out a biological procedure, biological reaction and/or a biological assay containing one or more inhibitors of this invention. The use of oligomers and/or polymers of this invention as additives in buffers or reagents. The inhibitors of the invention can also be attached to surfaces to provide for removal of nucleases from media, solutions or other liquids in contact with the solid.
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公开(公告)号：US07256259B2
公开(公告)日：2007-08-14
申请号：US10930702
申请日：2004-08-30
CPC分类号： C07K1/1077 , C07F9/4866 , C07F9/5004 , C07F9/5022 , C07F9/5054 , C07K1/082 , C07K1/1072 , Y10S530/81
摘要： The present invention is a method for a covalent ligation of one or more molecules to one or more surfaces, that is site-specific and both rapid and high yielding. The covalent ligation to the surface is based on the reaction of an azide and a phosphinothioester to form an amide bond. The method of the invention is particularly well-suited to the immobilization of peptides, proteins or protein fragments to surfaces.
摘要翻译： 本发明是一种或多种分子与一个或多个表面共价连接的方法，其是位点特异性的并且快速和高产率。 与表面的共价连接基于叠氮化物和膦硫代酯的反应以形成酰胺键。 本发明的方法特别适用于将肽，蛋白质或蛋白质片段固定在表面上。
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公开(公告)号：US08410247B2
公开(公告)日：2013-04-02
申请号：US12546249
申请日：2009-08-24
申请人： Ronald T. Raines , Annie Tam , Matthew B. Soellner
发明人： Ronald T. Raines , Annie Tam , Matthew B. Soellner
IPC分类号： C07C231/10 , C07F9/50 , C07K1/02 , C07K1/04
CPC分类号： C07K1/082 , C07F9/5004 , C07F9/5022 , C07K1/086
摘要： Water soluble reagents and methods for the formation of an amide bond between a phosphinothioester and an azide in an aqueous medium. The phosphinothioester is generated using a water-soluble phosphinothiol reagent. This reaction allows formation of an amide bond between a wide variety of chemical species including amino acids, peptides or protein fragments in an aqueous solution. Of particular interest, this reaction allows for the formation of an amide bond in a physiological setting. In a specific embodiment, this invention provides reagents and methods for peptide ligation in an aqueous medium. The reaction eliminates the need for a cysteine residue and is traceless leaving no residual atoms in the ligated peptide product.
摘要翻译： 水溶性试剂和在水性介质中在膦硫基酯和叠氮化物之间形成酰胺键的方法。 使用水溶性硫代硫醇试剂产生膦硫代酯。 该反应允许在各种各样的化学物质（包括水溶液中的氨基酸，肽或蛋白质片段）之间形成酰胺键。 特别令人感兴趣的是，该反应允许在生理环境中形成酰胺键。 在具体实施方案中，本发明提供了用于在水性介质中肽连接的试剂和方法。 该反应消除了对半胱氨酸残基的需要，并且在连接的肽产物中没有残留的原子。
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公开(公告)号：US20100048866A1
公开(公告)日：2010-02-25
申请号：US12546249
申请日：2009-08-24
申请人： Ronald T. Raines , Annie Tam , Matthew B. Soellner
发明人： Ronald T. Raines , Annie Tam , Matthew B. Soellner
IPC分类号： C07K1/02 , C07F9/28 , C07F9/02 , C07D265/30
CPC分类号： C07K1/082 , C07F9/5004 , C07F9/5022 , C07K1/086
摘要： Water soluble reagents and methods for the formation of an amide bond between a phosphinothioester and an azide in an aqueous medium. The phosphinothioester is generated using a water-soluble phosphinothiol reagent. This reaction allows formation of an amide bond between a wide variety of chemical species including amino acids, peptides or protein fragments in an aqueous solution. Of particular interest, this reaction allows for the formation of an amide bond in a physiological setting. In a specific embodiment, this invention provides reagents and methods for peptide ligation in an aqueous medium. The reaction eliminates the need for a cysteine residue and is traceless leaving no residual atoms in the ligated peptide product.
摘要翻译： 水溶性试剂和在水性介质中在膦硫基酯和叠氮化物之间形成酰胺键的方法。 使用水溶性硫代硫醇试剂产生膦硫代酯。 该反应允许在各种各样的化学物质（包括水溶液中的氨基酸，肽或蛋白质片段）之间形成酰胺键。 特别令人感兴趣的是，该反应允许在生理环境中形成酰胺键。 在具体实施方案中，本发明提供了用于在水性介质中肽连接的试剂和方法。 该反应消除了对半胱氨酸残基的需要，并且在连接的肽产物中没有残留的原子。
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公开(公告)号：US09758569B2
公开(公告)日：2017-09-12
申请号：US11807270
申请日：2007-05-25
CPC分类号： C07K14/78 , C07K5/0821 , C07K14/001
摘要： Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly)n, where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.
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公开(公告)号：US08293872B2
公开(公告)日：2012-10-23
申请号：US13243373
申请日：2011-09-23
IPC分类号： C07K1/00
摘要： This invention relates to cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex. Also disclosed is the 3-D structure of the hRI•RNase 1 complex and methods for designing the RNase 1 variants.
摘要翻译： 本发明涉及通过分析由RNase1 hRI复合物的三维（3-D）原子结构定义的核糖核酸酶1和人核糖核酸酶抑制剂（hRI）之间的相互作用而鉴定的人核糖核酸酶1（核糖核酸酶1）的细胞毒性变体。 还公开了hRI·RNase 1复合物的3-D结构和用于设计RNA酶1变体的方法。
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