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1.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：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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公开(公告)号：US06538072B2
公开(公告)日：2003-03-25
申请号：US09888098
申请日：2001-06-22
IPC分类号： C08F830
CPC分类号： B01J31/2404 , B01J19/0046 , B01J31/2265 , B01J2219/00497 , B01J2219/005 , B01J2219/00585 , B01J2219/00596 , B01J2219/00603 , B01J2219/00605 , B01J2219/0061 , B01J2219/00637 , B01J2219/00722 , B01J2219/00738 , B01J2231/14 , B01J2531/821 , C07B2200/11 , C07F15/002 , C07F15/0046 , C08F10/00 , C40B40/14 , C08F2/38 , C08F4/80
摘要： A method of preparing a multivalent array that includes: polymerizing at least one monomer comprising at least one polymerizable group and at least one latent reactive group in the presence of a metal carbene catalyst to form a polymer template comprising at least one latent reactive group; and combining the polymer template with at least one functionalizing reagent comprising at least one reactive group under conditions effective to react the latent reactive group of the polymer template with the reactive group of the functionalizing reagent to form a multivalent array.
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公开(公告)号：US06271315B1
公开(公告)日：2001-08-07
申请号：US09335430
申请日：1999-06-17
IPC分类号： C08F830
CPC分类号： B01J31/2404 , B01J19/0046 , B01J31/2265 , B01J2219/00497 , B01J2219/005 , B01J2219/00585 , B01J2219/00596 , B01J2219/00603 , B01J2219/00605 , B01J2219/0061 , B01J2219/00637 , B01J2219/00722 , B01J2219/00738 , B01J2231/14 , B01J2531/821 , C07B2200/11 , C07F15/002 , C07F15/0046 , C08F10/00 , C40B40/14 , C08F2/38 , C08F4/80
摘要： A method of preparing a multivalent array that includes: polymerizing at least one monomer comprising at least one polymerizable group and at least one latent reactive group in the presence of a metal carbene catalyst to form a polymer template comprising at least one latent reactive group; and combining the polymer template with at least one functionalizing reagent comprising at least one reactive group under conditions effective to react the latent reactive group of the polymer template with the reactive group of the functionalizing reagent to form a multivalent array.
摘要翻译： 一种制备多价阵列的方法，其包括：在金属卡宾催化剂的存在下聚合至少一种包含至少一个可聚合基团和至少一个潜在反应性基团的单体以形成包含至少一个潜在反应性基团的聚合物模板; 以及在有效使聚合物模板的潜在反应性基团与官能化试剂的反应性基团反应形成多价阵列的条件下，将聚合物模板与至少一种包含至少一个反应性基团的官能化试剂组合。
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7.发明申请Methods and Reagents for Regulation of Cellular Responses in Biological Systems 审中-公开生物系统细胞响应调控方法与试剂公开(公告)号：US20100104585A1
公开(公告)日：2010-04-29
申请号：US12571983
申请日：2009-10-01
IPC分类号： A61K39/395
CPC分类号： A61K31/70 , A61K31/74 , A61K38/178 , B82Y30/00 , G01N33/5005
摘要： Multivalent ligands which carry or display at least one recognition element (RE), and preferably a plurality of recognition elements, for binding directly or indirectly to cells or other biological particles or more generally by binding to any biological molecule. The multivalent ligands provided can function for binding or targeting to any biological particle or molecule and particularly to targeting of cells or cell types or viruses, for cell aggregation and for macromolecular assembly of biological macromolecules. The multivalent ligands of this invention are applicable for creating scaffolds (assemblies) of chemical or biological species, including without limitation, antigens, epitopes, ligand binding groups, ligands for cell receptors and various macromolecules. In these scaffolds, the number, spacing, relative positioning and relative orientation of recognition elements can be controlled. The invention also relates to methods for aggregating biological particles and macromolecules and for modulating biological response employing the multivalent ligands provided.
摘要翻译： 携带或显示至少一种识别元件（RE）的多价配体，并且优选多个识别元件，用于直接或间接地结合细胞或其他生物颗粒，或更一般地通过结合任何生物分子。 所提供的多价配体可用于结合或靶向任何生物颗粒或分子，特别是靶向细胞或细胞类型或病毒，用于细胞聚集和生物大分子的大分子装配。 本发明的多价配体适用于生成化学或生物物种的支架（组件），包括但不限于抗原，表位，配体结合基团，细胞受体配体和各种大分子。 在这些支架中，可以控制识别元件的数量，间距，相对定位和相对定向。 本发明还涉及聚集生物颗粒和大分子的方法以及使用所提供的多价配体来调节生物反应的方法。
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公开(公告)号：US08062890B2
公开(公告)日：2011-11-22
申请号：US11504573
申请日：2006-08-15
CPC分类号： C12N5/0068 , C12N2503/02 , C12N2535/10 , G01N33/569 , G01N2610/00
摘要： A method for the construction of arrays from self-assembling monolayers is described. The arrays have particular utility for the screening of peptides ligands that can foster the growth of cells in culture. This technique has been used to identify peptide ligands that foster the growth of human stem cells, which otherwise require an extracellular matrix in order to grow in an undifferentiated state. This also makes possible an assay to identify other such peptides.
摘要翻译： 描述了用于从自组装单层构建阵列的方法。 阵列对于能够促进培养细胞生长的肽配体的筛选具有特别的用途。 已经使用这种技术鉴定促进人类干细胞生长的肽配体，否则需要细胞外基质以在未分化状态下生长。 这也使鉴定其他这样的肽成为可能。
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9.发明授权Methods and reagents for capping ruthenium or osmium carbene-catalyzed ROMP products 有权用于封盖钌或锇卡因催化的ROMP产品的方法和试剂公开(公告)号：US06291616B1
公开(公告)日：2001-09-18
申请号：US09336121
申请日：1999-06-17
IPC分类号： C08F426
CPC分类号： C08F10/00 , B01J19/0046 , B01J31/1805 , B01J31/2208 , B01J31/2265 , B01J31/2273 , B01J31/2295 , B01J31/2404 , B01J2219/00497 , B01J2219/005 , B01J2219/00585 , B01J2219/00596 , B01J2219/00603 , B01J2219/00605 , B01J2219/0061 , B01J2219/00637 , B01J2219/00722 , B01J2219/00738 , B01J2231/14 , B01J2531/821 , B01J2531/825 , C07B2200/11 , C07F15/002 , C07F15/0046 , C40B40/14 , C08F4/80 , C08F2/38
摘要： Methods of preparing a telechelic polymer (mono- or bi-telechelic) that use a ruthenium or osmium carbene catalyst and a capping agent, at least one of which is functionalized.
摘要翻译： 制备使用钌或锇卡因催化剂和封端剂的遥爪聚合物（单 - 或双遥爪）的方法，其中至少一种被官能化。
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公开(公告)号：US6022859A
公开(公告)日：2000-02-08
申请号：US970833
申请日：1997-11-14
CPC分类号： C07K14/4711 , C07K5/1019 , A61K38/00
摘要： A .beta.-amyloid inhibitor is disclosed. In one embodiment, this inhibitor comprises a recognition element that interacts specifically with .beta.-amyloid peptide and a disrupting element that alters .beta.-amyloid aggregation. In a preferable form of the present invention, the inhibitor is a peptide.
摘要翻译： 公开了β-淀粉样蛋白抑制剂。 在一个实施方案中，该抑制剂包含与β-淀粉样蛋白肽特异性相互作用的识别元件和改变β-淀粉样蛋白聚集的破坏性元件。 在本发明的优选形式中，抑制剂是肽。
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