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1. 发明申请

US20110275062A1 Systems And Methods For Integrating A Single DNA Molecule Into A Molecular Electronic Device 审中-公开
标题翻译：将单个DNA分子整合到分子电子装置中的系统和方法
公开(公告)号：US20110275062A1
公开(公告)日：2011-11-10
申请号：US12955310
申请日：2010-11-29
申请人： Xuefeng Guo , Colin Nuckolls , James Hone , Alon Gorodetsky , Jacqueline K. Barton
发明人： Xuefeng Guo , Colin Nuckolls , James Hone , Alon Gorodetsky , Jacqueline K. Barton
IPC分类号： C12Q1/68 , B05D5/12 , C23F1/02 , G01R27/28 , H01L51/30 , G01N33/68 , B05D3/00 , B82Y99/00
CPC分类号： H01L51/0001 , B82Y10/00 , G01N27/04 , G01N33/5308 , G01N33/54373 , H01L51/0049 , H01L51/0093 , H01L51/0595
摘要： The disclosed subject matter provides a techniques for precisely and/or functionally cutting carbon nanotubes, e.g., single walled carbon nanotubes (“SWNTs”) and integrating a single nucleic acid molecule (e.g., a DNA molecule) into a gap formed into the carbon nanotubes. In one aspect, a method of fabricating a molecular electronic device includes disposing a SWNT on a base layer, forming a gap in the SWNT using a lithographic process, and disposing a single DNA strand across the gap so that each end of the nucleic acid contacts a gap termini. The disclosed subject matter also provides techniques for measuring the electrical properties (charge transport) of a DNA molecule which is integrated into an SWNT. Furthermore, a molecular electronic device including an SWNT with an integrated nucleic acid molecule is disclosed.
摘要翻译：所公开的主题提供了用于精确和/或功能性地切割碳纳米管的技术，例如单壁碳纳米管（“SWNT”）并将单个核酸分子（例如，DNA分子）整合到形成碳纳米管的间隙中。一方面，制造分子电子器件的方法包括在基底层上设置SWNT，使用光刻工艺在SWNT中形成间隙，并且在间隙上设置单个DNA链，使得核酸的每个末端接触一个差距终点。所公开的主题还提供了用于测量整合到SWNT中的DNA分子的电特性（电荷转移）的技术。此外，公开了包含具有整合的核酸分子的SWNT的分子电子器件。

2. 发明授权

US08859533B2 Metalloinsertor complexes targeted to DNA mismatches 有权
标题翻译：金属支架复合物靶向DNA错配
公开(公告)号：US08859533B2
公开(公告)日：2014-10-14
申请号：US13511642
申请日：2012-05-10
申请人： Jacqueline K. Barton , Alexis Komor , Curtis J. Schneider , Alyson Weidmann , Russell Ernst
发明人： Jacqueline K. Barton , Alexis Komor , Curtis J. Schneider , Alyson Weidmann , Russell Ernst
IPC分类号： A61K31/555
CPC分类号： C07F15/008 , C07D241/36 , C07F15/0053
摘要： A composition including a Rh or Ru metalloinsertor complex specifically targets mismatch repair (MMR)-deficient cells. Selective cytotoxicity is induced in MMR-deficient cells upon uptake of the inventive metalloinsertor complexes.
摘要翻译：包含Rh或Ru金属离子复合物的组合物特异性靶向错配修复（MMR）缺陷型细胞。在本发明金属介导复合物摄取后，在MMR缺陷细胞中诱导选择性细胞毒性。

3. 发明授权

US5439794A Mixed ligand complexes and uses thereof as binding agents to DNA 失效
标题翻译：混合配体配合物及其作为DNA结合剂的用途
公开(公告)号：US5439794A
公开(公告)日：1995-08-08
申请号：US843315
申请日：1992-02-28
申请人： Jacqueline K. Barton
发明人： Jacqueline K. Barton
IPC分类号： C07D471/04 , C07F3/00 , C07F15/00 , C07F15/06 , C07H21/00 , C07H23/00 , C12Q1/68 , C07H21/04 , C07H21/02
CPC分类号： C07H21/00 , C07D471/04 , C07F15/0013 , C07F15/0053 , C07F15/008 , C07F15/065 , C07F3/003 , C07H23/00 , C12Q1/68 , C12Q1/6816
摘要： This invention concerns a coordination complex or salt thereof which is spectroscopically or photoactively determinable when bound to DNA having the formula ##STR1## wherein M is a suitable transition metal and each of R.sub.1, R.sub.2 and R.sub.3 is ethylenediamine or a substituted derivative thereof, bipyridine or a substituted derivative thereof, phenanthroline or a substituted derivative thereof, diazfluorene-9-one or a substituted derivative thereof, phenanthrenequinonediimine or a substituted derivative thereof; wherein R.sub.1, R.sub.2 and R.sub.3 are bound to M by coordination bonds wherein R.sub.1 and R.sub.2 are the same and both are different from R.sub.3. The invention also concerns a method of labeling DNA with the coordination complex, a DNA molecule labeled with the coordination complex, a method of selectively labeling DNA conformation with the coordination complex and a method of detecting the presence of a conformation present in a double stranded DNA.
摘要翻译：本发明涉及一种配位络合物或其盐，当与结合式为“IMAGE”的DNA结合时，其光谱或光活性可确定，其中M为合适的过渡金属，R 1，R 2和R 3各自为乙二胺或其取代的衍生物，联吡啶或取代衍生物，菲咯啉或其取代的衍生物，二氮杂芴-9-酮或其取代衍生物，菲醌亚胺或其取代的衍生物; 其中R1，R2和R3通过配位键与M结合，其中R 1和R 2相同并且两者都不同于R 3。本发明还涉及用配位络合物标记DNA的方法，用配位络合物标记的DNA分子，用配位络合物选择性标记DNA构象的方法和检测双链DNA中存在的构象的方法。

4. 发明授权

US06306601B1 Detection and treatment of duplex polynucleotide damage 有权
标题翻译：检测和处理双链多核苷酸损伤
公开(公告)号：US06306601B1
公开(公告)日：2001-10-23
申请号：US09447447
申请日：1999-11-22
申请人： Jacqueline K. Barton , Brian A. Jackson , Brian P. Hudson
发明人： Jacqueline K. Barton , Brian A. Jackson , Brian P. Hudson
IPC分类号： C12Q168
CPC分类号： C07F15/008
摘要： Duplex polynucleotides containing damage or errors are detected with hindered intercalating compounds which are capable of intercalating only in the presence of such damage or error. Conditions characterized by the presence of polynucleotide errors or damage are treated with such compounds that are capable of catalyzing polynucleotide cleavage with light. Suitable compound include compounds of the formula: Rh(R1)(R2)(R3)3+ where R1 and R2 are each indepenently aryl, heteroaryl, substituted aryl or substituted heteroaryl of 1 to 5 rings, and R3 is a group of the formula where x and z are each independently an interger from 1 to 4 and y is an interger from 1 to 2, and R4, R5, and R6 are independently H—, halo, HO—, H2N—, CN—, O2N—, HS—, O3S—, O3SO—, —COOH, —CONH2, R, RO—, RNH—, RaRbN—, RO3SO—, RO3SO—, —COOR, —CONHR, or —CONHRaRbwhere R, Ra and Rb are each independently lower alkyl, cycloalkyl, lower alkenyl, lower alkynyl, or phenyl, or two R4, R5, or R6 together form a fused aryl ring.
摘要翻译：含有损伤或错误的双链多核苷酸用受阻的插入化合物检测，只能在存在这种损伤或错误的情况下插入。以多核苷酸错误或损伤存在为特征的条件用能够用光催化多核苷酸切割的化合物处理。合适的化合物包括下式的化合物：其中R 1和R 2各自独立地为1至5个环的芳基，杂芳基，取代的芳基或取代的杂芳基，并且R 3是式的基团，x和z各自独立地为1至4的整数并且y是1至2的整数，R4，R5和R6独立地为H，卤素，HO-，H2N-，CN-，O2N-，HS-，O3S-，O3SO-，-COOH，-CONH2 ，R，RO-，RNH-，RaRbN-，RO3SO-，RO3SO-，-COOR，-CONHR或-CONHRaRb，其中R，Ra和Rb各自独立地为低级烷基，环烷基，低级烯基，低级炔基或苯基，或两个R 4，R 5或R 6一起形成稠合的芳基环。

5. 发明授权

US5225556A Chemical probes for left-handed DNA and for A-DNA; chiral metal complexes as Z-specific antitumor agents and as double strand cleavers 失效
标题翻译：用于左旋DNA和A-DNA的化学探针; 手性金属络合物作为Z-特异性抗肿瘤剂和双链切割
公开(公告)号：US5225556A
公开(公告)日：1993-07-06
申请号：US927865
申请日：1992-08-10
申请人： Jacqueline K. Barton
发明人： Jacqueline K. Barton
IPC分类号： C07D471/04 , C07F15/06 , C07H21/00 , C07H23/00 , C12Q1/68
CPC分类号： C07D471/04 , C07F15/065 , C07H21/00 , C07H23/00 , C12Q1/68 , C12Q1/6816 , Y10S435/81
摘要： This invention concerns a coordination complex and salts and optically resolved enantiomers thereof, of the formula (R).sub.3 --M, wherein R comprises 1,10-phenanthroline or a substituted derivative thereof, M comprises a suitable transition metal, e.g. ruthenium(II), RHODIUM(III) or cobalt(III), and R is bonded to M by a coordination bond.The complexes of this invention are useful in methods for labeling, nicking and cleaving DNA. The lambda enantiomer of complexes of this invention is useful in methods for specifically labeling, detecting, nicking and cleaving Z-DNA or A-DNA.The complexes may also be used in a method for killing tumor cells and may be combined with a pharmaceutically acceptable carrier to form a pharmaceutical composition for the treatment of tumor cells in a subject. The invention further concerns methods for treating a subject affilicted with tumor cells.
摘要翻译：本发明涉及式（R）3-M的配位络合物及其盐和光学拆分的对映异构体，其中R包括1,10-菲咯啉或其取代的衍生物，M包括合适的过渡金属，钌（II），铑（III）或钴（III），R通过配位键与M键合。本发明的复合物可用于标记，切口和切割DNA的方法。本发明络合物的λ对映异构体可用于特异性标记，检测，切割和切割Z-DNA或A-DNA的方法。复合物也可以用于杀死肿瘤细胞的方法，并且可以与药学上可接受的载体组合以形成用于治疗受试者中的肿瘤细胞的药物组合物。本发明还涉及用于治疗患有肿瘤细胞的受试者的方法。

6. 发明授权

US5157032A Mixed ligand complexes and uses thereof as binding agents and probes to DNA 失效
标题翻译：混合配体配合物及其作为结合剂和DNA探针的用途
公开(公告)号：US5157032A
公开(公告)日：1992-10-20
申请号：US539930
申请日：1990-06-18
申请人： Jacqueline K. Barton
发明人： Jacqueline K. Barton
IPC分类号： C07D471/04 , C07F15/06 , C07H21/00 , C07H23/00 , C12Q1/68
CPC分类号： C07D471/04 , C07F15/065 , C07H21/00 , C07H23/00 , C12Q1/68 , C12Q1/6816 , Y10S514/885
摘要： This invention concerns a coordination complex or salt thereof which is spectroscopically or photoactively determinable when bound to DNA having the formula ##STR1## wherein M is a suitable transition metal and each of R.sub.1, R.sub.2 and R.sub.3 is ethylenediamine, bipyridine, phenanthroline, diazafluorene-9-one or a substituted derivative thereof, or phenanthrenequinonediimine or a substituted derivative thereof, dypyridophenazine or a substituted derivative thereof; wherein R.sub.1, R.sub.2 and R.sub.3 are bound to M by coordination bonds; provided that at least one of R1, R2 or R3 is dypyridophenazine or a substituted derivative thereof. The invention also concerns a labeled DNA probe which comprises the complex covalently bound to the DNA probe. Further the invention concerns a method of detecting the presence in a sample a target DNA of interest which comprises contacting the sample containing the target DNA with a complementary labeled DNA probe under hybridizing conditions and measuring the resulting luminescense emitted from the labeled DNA probe, a change in the luminescense as compared with the luminescense in the absence of the sample indicating the presence of the target DNA.
摘要翻译：本发明涉及一种配位络合物或其盐，其在与具有式IMA的DNA结合时光谱或光活性可测定，其中M为合适的过渡金属，R 1，R 2和R 3各自为乙二胺，联吡啶，菲咯啉，二氮杂芴-9 或其取代衍生物，或菲醌亚胺或其取代衍生物，二吡啶并吩嗪或其取代的衍生物; 其中R1，R2和R3通过配位键与M结合; 条件是R 1，R 2或R 3中的至少一个是二吡啶并吩嗪或其取代的衍生物。本发明还涉及标记的DNA探针，其包含共价结合DNA探针的复合物。此外，本发明涉及一种检测样品中存在感兴趣的靶DNA的方法，其包括在杂交条件下使包含靶DNA的样品与补体标记的DNA探针接触，并测量从标记的DNA探针发射的所得发射亮度，变化在不存在样品表明靶DNA存在的情况下与发光相比较。

7. 发明授权

US4699978A Site-specific chiral ruthenium (II) and cobalt (III) antitumor agents 失效
标题翻译：位点特异性手性钌（II）和钴（III）抗肿瘤剂
公开(公告)号：US4699978A
公开(公告)日：1987-10-13
申请号：US693019
申请日：1985-01-18
申请人： Jacqueline K. Barton
发明人： Jacqueline K. Barton
IPC分类号： C07F15/00 , C07F15/06 , C12Q1/68 , A61K33/24 , C07D471/04 , C07H21/00
CPC分类号： C12Q1/68 , C07F15/0053 , C07F15/065 , C12Q1/6816
摘要： This invention concerns a coordination complex of the formula (R).sub.2 --M--(Y).sub.2 wherein M comprises a suitable transition metal, e.g. cobalt or ruthenium, R comprises 1,10-phenanthroline or a substituted derivative thereof, Y comprises a labile ligand, e.g. chloride, tartrate, malonate or ascorbate ion and R and Y are bonded to M by coordination bonds.A complex of this invention may be used for covalently labeling DNA with a complex of the formula (R).sub.2 --M, wherein R and M are as previously defined. A complex of this invention which contains cobalt may also be used in a method for nicking DNA by effecting single-stranded scission of at least one phosphodiester bond of the DNA with ultraviolet radiation.A complex of this invention is further useful in a method for killing tumor cells. A pharmaceutical composition for the treatment of tumor cells in a subject may be prepared containing an effective anti-tumor amount of a complex of this invention and a pharmaceutically acceptable carrier. Such a composition may be used for treating a subject afflicted with tumor cells so as to cause regression of the tumor cells.
摘要翻译：本发明涉及式（R）2-M-（Y）2的配位络合物，其中M包括合适的过渡金属，例如钴或钌，R包括1,10-菲咯啉或其取代衍生物，Y包括不稳定的配体，例如，氯化物，酒石酸盐，丙二酸盐或抗坏血酸盐离子，R和Y通过配位键与M键合。本发明的复合物可用于与式（R）2-M的复合物共价标记DNA，其中R和M如前所定义。含有钴的本发明的复合物也可以用于通过用紫外线辐射进行DNA的至少一个磷酸二酯键的单链断裂来切割DNA的方法。本发明的复合物还可用于杀死肿瘤细胞的方法。可以制备用于治疗受试者中的肿瘤细胞的药物组合物，其含有有效的抗肿瘤量的本发明的复合物和药学上可接受的载体。这样的组合物可以用于治疗患有肿瘤细胞的受试者，以使肿瘤细胞消退。

8. 发明授权

US07345172B2 Methods and compositions for detecting polynucleotide duplex damage and errors 有权
标题翻译：检测多核苷酸双链体损伤和错误的方法和组合物
公开(公告)号：US07345172B2
公开(公告)日：2008-03-18
申请号：US10974474
申请日：2004-10-26
申请人： Jacqueline K. Barton , Henrik Junicke
发明人： Jacqueline K. Barton , Henrik Junicke
IPC分类号： C07D242/36
CPC分类号： C07F15/008 , A61K41/0042 , A61K49/0017 , A61K49/0019 , C12Q1/6827 , C12Q1/6883 , C12Q2600/156 , C12Q2563/173
摘要： In accordance with the present invention there is provided a new class of sterically demanding metallo-intercalators. These compounds intercalate between bases in a duplex polynucleotide, but only where the bases are not fully complementary, for example, where there is a base-pair mismatch. The compounds are sufficiently sterically demanding that intercalation between bases in fully complementary duplexes does not occur to a significant degree. These mismatch intercalators are useful for detecting DNA and RNA defects, for diagnosing disorders characterized by the presence or increase in DNA and/or RNA defects, and for treating such disorders. Further, the compounds are capable of catalyzing photolytic cleavage of nucleic acids at relatively long wavelengths, and under normal sunlight.
摘要翻译：根据本发明，提供了一类新颖的空间要求的金属 - 嵌入剂。这些化合物插入双链多核苷酸的碱基之间，但是仅在碱不完全互补的情况下，例如，其中存在碱基对失配。化合物足够空间要求在完全互补双链体中的碱基之间的嵌入不会显着地发生。这些错配嵌入剂可用于检测DNA和RNA缺陷，用于诊断以DNA和/或RNA缺陷的存在或增加为特征的疾病，以及用于治疗这些疾病。此外，化合物能够在相对长的波长和正常的阳光下催化核酸的光解裂解。

9. 发明授权

US06649350B2 Electrochemical sensor using intercalative, redox-active moieties 有权
公开(公告)号：US06649350B2
公开(公告)日：2003-11-18
申请号：US09953242
申请日：2001-09-13
申请人： Jacqueline K. Barton , Elizabeth M. Boon , Shana O. Kelley , Michael G. Hill
发明人： Jacqueline K. Barton , Elizabeth M. Boon , Shana O. Kelley , Michael G. Hill
IPC分类号： C12Q168
CPC分类号： C12Q1/6827 , B82Y30/00 , C12Q1/6825 , C12Q1/6837 , C12Q2565/607 , C12Q2563/113 , C12Q2563/173
摘要： Compositions and methods for electrochemical detection and localization of genetic point mutations, common DNA lesions and other base-stacking perturbations within oligonucleotide duplexes adsorbed onto electrodes and their use in biosensing technologies are described. An intercalative, redox-active moiety (such as an intercalator or nucleic acid-binding protein) is adhered and/or crosslinked to immobilized DNA duplexes at different separations from an electrode and probed electrochemically in the presence or absence of a non-intercalative, redox-active moiety. Interruptions in DNA-mediated electron-transfer caused by base-stacking perturbations, such as mutations or binding of a protein to its recognition site are reflected in a difference in electrical current, charge and/or potential.

10. 发明授权

US06221586B1 Electrochemical sensor using intercalative, redox-active moieties 失效
标题翻译：使用插入型氧化还原活性部分的电化学传感器
公开(公告)号：US06221586B1
公开(公告)日：2001-04-24
申请号：US09056995
申请日：1998-04-08
申请人： Jacqueline K. Barton , Michael G. Hill , Shana O. Kelley
发明人： Jacqueline K. Barton , Michael G. Hill , Shana O. Kelley
IPC分类号： C12Q168
CPC分类号： C12Q1/6825 , B82Y5/00 , B82Y30/00 , C12Q1/6827 , C12Q1/6837 , C12Q2563/173 , C12Q2563/113 , C12Q2565/607
摘要： Compositions and methods for electrochemical detection and localization of genetic point mutations and other base-stacking perturbations within oligonucleotide duplexes adsorbed onto electrodes and their use in biosensing technologies are described. An intercalative, redox-active moiety (such as an intercalator or nucleic acid-binding protein) is adhered and/or crosslinked to immobilized DNA duplexes at different separations from an electrode and probed electrochemically in the presence or absence of a non-intercalative, redox-active moiety. Interruptions in DNA-mediated electron-transfer caused by base-stacking perturbations, such as mutations or binding of a protein to its recognition site are reflected in a difference in electrical current, charge and/or potential.
摘要翻译：描述了吸附在电极上的寡核苷酸双链体内的遗传点突变和其他碱基堆叠扰动的电化学检测和定位及其在生物传感技术中的应用的组合物和方法。插入的氧化还原活性部分（例如嵌入剂或核酸结合蛋白）在与电极的不同分离处固定和/或交联固定的DNA双链体并且在存在或不存在非插入式氧化还原的情况下电化学研究活性部分。由碱基堆叠扰动导致的DNA介导的电子转移的中断，例如蛋白质与其识别位点的突变或结合反映在电流，电荷和/或电位的差异中。

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