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1. 发明授权

US06770486B1 Optimization of ligand affinity for RNA targets using mass spectrometry 有权
标题翻译：使用质谱法优化RNA靶标的配体亲和力
公开(公告)号：US06770486B1
公开(公告)日：2004-08-03
申请号：US09499875
申请日：2000-02-08
申请人： Richard Griffey , Steven Hofstadler , Jared J. Drader , Kristin S. Lowery , Venkatraman Mohan
发明人： Richard Griffey , Steven Hofstadler , Jared J. Drader , Kristin S. Lowery , Venkatraman Mohan
IPC分类号： G01N2400
CPC分类号： H01J49/0031 , H01J49/00 , Y10T436/24
摘要： The present invention provides methods for the identification ligand compounds that bind to target molecules such as proteins or structured RNA with as little as millimolar (mM) affinity using mass spectrometry. The methods may be used to determine the mode of binding interaction between two or more of these ligand compounds to the target as well as their relative affinities. Also provided are methods for designing compounds having greater affinity to a target molecule by identifying two or more ligands using mass spectrometry methods of the invention and linking the ligands together to form a novel compound.
摘要翻译：本发明提供了使用质谱法鉴定与目标分子如蛋白质或结构化RNA结合至少达到毫摩尔（mM）亲和力的配体化合物的方法。这些方法可用于确定两种或多种这些配体化合物与靶标之间的结合相互作用的模式以及它们的相对亲和力。还提供了通过使用本发明的质谱方法鉴定两个或更多个配体并将配体连接在一起形成新化合物来设计对靶分子具有更高亲和力的化合物的方法。

2. 发明授权

US08188011B1 Optimization of ligand affinity for RNA targets using mass spectrometry 有权
标题翻译：使用质谱法优化RNA靶标的配体亲和力
公开(公告)号：US08188011B1
公开(公告)日：2012-05-29
申请号：US09573479
申请日：2000-05-16
申请人： Richard Griffey , Steven Hofstadler , Jared J. Drader , Kristin S. Lowery
发明人： Richard Griffey , Steven Hofstadler , Jared J. Drader , Kristin S. Lowery
IPC分类号： C40B30/00
CPC分类号： C12Q1/68 , C12Q2565/627 , Y10T436/24
摘要： The present invention provides methods for the identification ligand compounds that bind to target molecules such as proteins or structured RNA with as little as millimolar (mM) affinity using mass spectrometry. The methods may be used to determine the mode of binding interaction between two or more of these ligand compounds to the target as well as their relative affinities. Also provided are methods for designing compounds having greater affinity to a target molecule by identifying two or more ligands using mass spectrometry methods of the invention and linking the ligands together to form a novel compound.
摘要翻译：本发明提供了使用质谱法鉴定与目标分子如蛋白质或结构化RNA结合至少达到毫摩尔（mM）亲和力的配体化合物的方法。这些方法可用于确定两种或多种这些配体化合物与靶标之间的结合相互作用的模式以及它们的相对亲和力。还提供了通过使用本发明的质谱方法鉴定两个或更多个配体并将配体连接在一起形成新化合物来设计对靶分子具有更高亲和力的化合物的方法。

3. 发明授权

US06969763B1 Molecular interaction sites of interleukin-2 RNA and methods of modulating the same 失效
标题翻译：白细胞介素-2 RNA的分子相互作用位点及其调控方法
公开(公告)号：US06969763B1
公开(公告)日：2005-11-29
申请号：US09310844
申请日：1999-05-12
申请人： David J. Ecker , Richard Griffey , Stanley T. Crooke , Ranga Sampath , Eric Swayze , Venkatraman Mohan , Steven Hofstadler , John McNeil
发明人： David J. Ecker , Richard Griffey , Stanley T. Crooke , Ranga Sampath , Eric Swayze , Venkatraman Mohan , Steven Hofstadler , John McNeil
IPC分类号： C07H21/04 , C07K14/54 , C07K14/55 , C40B30/02 , C40B50/02 , G06F19/00
CPC分类号： C40B50/02 , C07H21/04 , C07K14/5406 , C07K14/55 , C40B30/02 , G06F19/14 , G06F19/16 , G06F19/28
摘要： Methods for the identification of compounds which modulate, either inhibit or stimulate, biomolecules are provided. Nucleic acids, especially RNAs are preferred substrates for such modulation. The present methods are particularly powerful in that they provide novel combinations of techniques which give rise to compounds, usually “small” organic compounds, which are highly potent modulators of RNA and other biomolecular activity. In accordance with preferred aspects of the invention, very large numbers of compounds may be tested essentially simultaneously to determine whether they are likely to interact with a molecular interaction site and modulate the activity of the biomolecule. Pharmaceuticals, veterinary drugs, agricultural chemicals, industrial chemicals, research chemicals and many other beneficial compounds may be identified in accordance with embodiments of this invention.
摘要翻译：提供了用于鉴定调节，抑制或刺激生物分子的化合物的方法。核酸，特别是RNA是用于这种调节的优选底物。本发明的方法特别强大，因为它们提供了引起化合物（通常是“小”）有机化合物的技术的新组合，其是RNA和其它生物分子活性的高效调节剂。根据本发明的优选方面，可以基本上同时测试非常大量的化合物以确定它们是否可能与分子相互作用位点相互作用并且调节生物分子的活性。根据本发明的实施方案，可以鉴定药物，兽药，农药，工业化学品，研究化学品和许多其它有益化合物。

4. 发明申请

US20080160512A1 Method for rapid detection and identification of bioagents 有权
标题翻译：快速检测和鉴定生物标签的方法
公开(公告)号：US20080160512A1
公开(公告)日：2008-07-03
申请号：US11233630
申请日：2005-09-21
申请人： David J. Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
发明人： David J. Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
IPC分类号： C12Q1/68 , G06F19/00
CPC分类号： C12Q1/689 , C12Q1/686 , C12Q2600/156 , C12Q2565/627
摘要： Method for detecting and identifying unknown bioagents, including bacteria, viruses and the like, by a combination of nucleic acid amplification and molecular weight determination using primers which hybridize to conserved sequence regions of nucleic acids derived from a bioagent and which bracket variable sequence regions that uniquely identify the bioagent. The result is a “base composition signature” (BCS) which is then matched against a database of base composition signatures, by which the bioagent is identified.
摘要翻译：通过核酸扩增和分子量测定的组合来检测和识别未知生物标签的方法，所述引物与衍生自生物制剂的核酸的保守序列区域杂交的引物以及独特的括号可变序列区域识别生物制剂。结果是“基本组成签名”（BCS），然后与基础组合签名的数据库进行匹配，通过该数据库识别生物标签。

5. 发明申请

US20060121520A1 Method for rapid detection and identification of bioagents 有权
公开(公告)号：US20060121520A1
公开(公告)日：2006-06-08
申请号：US11331987
申请日：2006-01-13
申请人： David Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
发明人： David Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
IPC分类号： C12Q1/68 , G06F19/00 , C07H21/04
CPC分类号： C12Q1/689 , C12Q1/686 , C12Q2600/156 , C12Q2565/627
摘要： Method for detecting and identifying unknown bioagents, including bacteria, viruses and the like, by a combination of nucleic acid amplification and molecular weight determination using primers which hybridize to conserved sequence regions of nucleic acids derived from a bioagent and which bracket variable sequence regions that uniquely identify the bioagent. The result is a “base composition signature” (BCS) which is then matched against a database of base composition signatures, by which the bioagent is identified.

6. 发明授权

US06342393B1 Methods and apparatus for external accumulation and photodissociation of ions prior to mass spectrometric analysis 失效
标题翻译：在质谱分析前离子的外部积聚和光离解的方法和装置
公开(公告)号：US06342393B1
公开(公告)日：2002-01-29
申请号：US09235528
申请日：1999-01-22
申请人： Steven Hofstadler , Richard Griffey
发明人： Steven Hofstadler , Richard Griffey
IPC分类号： G01N3300
CPC分类号： H01J49/0059 , Y10T436/143333 , Y10T436/24
摘要： The present invention discloses novel methods and apparatuses for mass spectrometry. In the methods and apparatuses of the invention, ions are accumulated in an ion reservoir and dissociated with coherent radiation prior to mass analysis. These methods and apparatuses are amenable to mass spectrometric analysis of biomolecules and are particularly usefuil for the sequencing of oligonucleotides, peptides and oligosaccharides.
摘要翻译：本发明公开了用于质谱的新颖的方法和装置。在本发明的方法和装置中，在质量分析之前，离子积聚在离子储存器中并与相干辐射分离。这些方法和装置适于生物分子的质谱分析，并且特别用于寡核苷酸，肽和寡糖的测序。

7. 发明授权

US06329146B1 Mass spectrometric methods for biomolecular screening 有权
标题翻译：用于生物分子筛选的质谱法
公开(公告)号：US06329146B1
公开(公告)日：2001-12-11
申请号：US09260310
申请日：1999-03-02
申请人： Stanley T. Crooke , Richard Griffey , Steven Hofstadler
发明人： Stanley T. Crooke , Richard Griffey , Steven Hofstadler
IPC分类号： C12Q168
CPC分类号： C12Q1/6816 , B01J2219/00702 , B01J2219/00722 , C12Q1/6806 , C12Q1/6811 , C40B40/06 , H01J49/004 , Y10T436/24 , C12Q2565/627 , C12Q2525/101 , C12Q2565/133 , C12Q2525/121 , C12Q2565/607
摘要： The present invention provides methods for the determination of the structure of biomolecular targets, as well as the site and nature of the interaction between ligands and biomolecular targets. The present invention also provides methods for the determination of the relative affinity of a ligand for the biomolecular target it interacts with. Also provided are methods for screening ligand or combinatorial libraries of compounds against one or more than one biological target molecules. The methods of the invention also allow determination of the relative binding affinity of combinatorial and other compounds for a biomolecular target. The present invention further provides methods for the use of mass modifying tags for screening multiple biomolecular targets. In a preferred embodiment, ligands which have great specificity and affinity for molecular interaction sites on biomolecules, especially RNA can be identified. In preferred embodiments, such identification can be made simultaneously with libraries of ligands.
摘要翻译：本发明提供了用于确定生物分子靶标的结构的方法，以及配体和生物分子靶标之间的相互作用的位点和性质。本发明还提供了确定配体与其相互作用的生物分子靶的相对亲和力的方法。还提供了用于筛选针对一种或多于一种生物靶分子的化合物的配体或组合文库的方法。本发明的方法还允许确定组合和其它化合物对于生物分子靶标的相对结合亲和力。本发明还提供使用质量修饰标签筛选多个生物分子靶标的方法。在优选的实施方案中，可以鉴定对生物分子，特别是RNA上的分子相互作用位点具有极大特异性和亲和力的配体。在优选的实施方案中，这种鉴定可以与配体文库同时进行。

8. 发明授权

US08211636B2 Mass spectrometric methods for biomolecular screening 有权
标题翻译：用于生物分子筛选的质谱法
公开(公告)号：US08211636B2
公开(公告)日：2012-07-03
申请号：US10608354
申请日：2003-06-27
申请人： Stanley T. Crook , Richard Griffey , Steven Hofstadler
发明人： Stanley T. Crook , Richard Griffey , Steven Hofstadler
IPC分类号： C12Q1/68 , C12P19/34 , G01N24/00 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6816 , B01J2219/00702 , B01J2219/00722 , C12Q1/6806 , C12Q1/6811 , C40B40/06 , H01J49/004 , Y10T436/24 , C12Q2565/627 , C12Q2525/101 , C12Q2565/133 , C12Q2525/121 , C12Q2565/607
摘要： The present invention provides methods for the determination of the structure of biomolecular targets, as well as the site and nature of the interaction between ligands and biomolecular targets. The present invention also provides methods for the determination of the relative affinity of a ligand for the biomolecular target it interacts with. Also provided are methods for screening ligand or combinatorial libraries of compounds against one or more than one biological target molecules. The methods of the invention also allow determination of the relative binding affinity of combinatorial and other compounds for a biomolecular target. The present invention further provides methods for the use of mass modifying tags for screening multiple biomolecular targets. In a preferred embodiment, ligands which have great specificity and affinity for molecular interaction sites on biomolecules, especially RNA can be identified. In preferred embodiments, such identification can be made simultaneously with libraries of ligands.
摘要翻译：本发明提供了用于确定生物分子靶标的结构的方法，以及配体和生物分子靶标之间的相互作用的位点和性质。本发明还提供了确定配体与其相互作用的生物分子靶的相对亲和力的方法。还提供了用于筛选针对一种或多于一种生物靶分子的化合物的配体或组合文库的方法。本发明的方法还允许确定组合和其它化合物对于生物分子靶标的相对结合亲和力。本发明还提供使用质量修饰标签筛选多个生物分子靶标的方法。在优选的实施方案中，可以鉴定对生物分子，特别是RNA上的分子相互作用位点具有极大特异性和亲和力的配体。在优选的实施方案中，这种鉴定可以与配体文库同时进行。

9. 发明申请

US20060275788A1 Method for rapid detection and identification of bioagents 有权
公开(公告)号：US20060275788A1
公开(公告)日：2006-12-07
申请号：US11331978
申请日：2006-01-13
申请人： David Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
发明人： David Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/689 , C12Q1/686 , C12Q2600/156 , C12Q2565/627
摘要： Method for detecting and identifying unknown bioagents, including bacteria, viruses and the like, by a combination of nucleic acid amplification and molecular weight determination using primers which hybridize to conserved sequence regions of nucleic acids derived from a bioagent and which bracket variable sequence regions that uniquely identify the bioagent. The result is a “base composition signature” (BCS) which is then matched against a database of base composition signatures, by which the bioagent is identified.

10. 发明授权

US07108974B2 Method for rapid detection and identification of bioagents 有权
公开(公告)号：US07108974B2
公开(公告)日：2006-09-19
申请号：US10156608
申请日：2002-05-24
申请人： David J. Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
发明人： David J. Ecker , Richard Griffey , Rangarajan Sampath , Steven Hofstadler , John McNeil
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02
CPC分类号： C12Q1/689 , C12Q1/686 , C12Q2600/156 , C12Q2565/627
摘要： Method for detecting and identifying unknown bioagents, including bacteria, viruses and the like, by a combination of nucleic acid amplification and molecular weight determination using primers which hybridize to conserved sequence regions of nucleic acids derived from a bioagent and which bracket variable sequence regions that uniquely identify the bioagent. The result is a “base composition signature” (BCS) which is then matched against a database of base composition signatures, by which the bioagent is identified.

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