CHIMERIC ZINC FINGER RECOMBINASES OPTIMIZED FOR CATALYSIS BY DIRECTED EVOLUTION
    1.
    发明申请
    CHIMERIC ZINC FINGER RECOMBINASES OPTIMIZED FOR CATALYSIS BY DIRECTED EVOLUTION 失效
    通过指导进化优化的CHIMERIC ZINC指纹重组

    公开(公告)号:US20100086532A1

    公开(公告)日:2010-04-08

    申请号:US12309096

    申请日:2007-07-05

    摘要: The present invention is directed to chimeric recombinases comprising a serine recombinase operatively linked to a zinc finger nucleotide binding domain such that the chimeric recombinase protein catalyzes site-specific recombination at a DNA site specifically bound by the zinc finger nucleotide binding domain. The serine recombinase can be one of several naturally occurring serine recombinases. The invention also includes nucleic acids encoding the chimeric recombinases, vectors including the nucleic acids, host cells transformed or transfected with the vectors, methods of using the chimeric recombinases to carry out recombination, methods of using substrate-linked protein evolution to generate additional chimeric recombinases, methods of using the chimeric recombinases for gene therapy, and pharmaceutical compositions.

    摘要翻译: 本发明涉及包含与锌指核苷酸结合结构域有效连接的丝氨酸重组酶的嵌合重组酶,使得嵌合重组酶蛋白在由锌指核苷酸结合结构域特异性结合的DNA位点处催化位点特异性重组。 丝氨酸重组酶可以是几种天然存在的丝氨酸重组酶之一。 本发明还包括编码嵌合重组酶的核酸,包括核酸的载体,用载体转化或转染的宿主细胞,使用嵌合重组酶进行重组的方法,使用底物连接蛋白进化产生另外的嵌合重组酶的方法 ,使用嵌合重组酶进行基因治疗的方法和药物组合物。

    Chimeric zinc finger recombinases optimized for catalysis by directed evolution
    2.
    发明授权
    Chimeric zinc finger recombinases optimized for catalysis by directed evolution 失效
    通过定向进化优化催化的嵌合锌指重组酶

    公开(公告)号:US08685687B2

    公开(公告)日:2014-04-01

    申请号:US12309096

    申请日:2007-07-05

    IPC分类号: C12N9/00

    摘要: The present invention is directed to chimeric recombinases comprising a serine recombinase operatively linked to a zinc finger nucleotide binding domain such that the chimeric recombinase protein catalyzes site-specific recombination at a DNA site specifically bound by the zinc finger nucleotide binding domain. The serine recombinase can be one of several naturally occurring serine recombinases. The invention also includes nucleic acids encoding the chimeric recombinases, vectors including the nucleic acids, host cells transformed or transfected with the vectors, methods of using the chimeric recombinases to carry out recombination, methods of using substrate-linked protein evolution to generate additional chimeric recombinases, methods of using the chimeric recombinases for gene therapy, and pharmaceutical compositions.

    摘要翻译: 本发明涉及包含与锌指核苷酸结合结构域有效连接的丝氨酸重组酶的嵌合重组酶,使得嵌合重组酶蛋白在由锌指核苷酸结合结构域特异性结合的DNA位点处催化位点特异性重组。 丝氨酸重组酶可以是几种天然存在的丝氨酸重组酶之一。 本发明还包括编码嵌合重组酶的核酸,包括核酸的载体,用载体转化或转染的宿主细胞,使用嵌合重组酶进行重组的方法,使用底物连接蛋白进化产生另外的嵌合重组酶的方法 ,使用嵌合重组酶进行基因治疗的方法和药物组合物。

    Tyrosine Bioconjugation through Aqueous Ene-Like Reactions
    4.
    发明申请
    Tyrosine Bioconjugation through Aqueous Ene-Like Reactions 失效
    通过水性类似反应的酪氨酸生物缀合

    公开(公告)号:US20120289682A1

    公开(公告)日:2012-11-15

    申请号:US13518353

    申请日:2010-12-23

    IPC分类号: C07K1/13 C07K1/00 C07D249/12

    摘要: A new and versatile class of cyclic diazodicarboxamides that reacts efficiently and selectively with phenols and the phenolic side chain of tyrosine through an Ene-like reaction is reported. This mild aqueous tyrosine ligation reaction works over a broad pH range and expands the repertoire of aqueous chemistries available for small molecule, peptide, and protein modification. The tyrosine ligation reactions are shown to be compatible with the labeling of native enzymes and antibodies in buffered aqueous solution. This reaction provides a novel synthetic approach to bispecific antibodies. This reaction will find broad utility in peptide and protein chemistry and in the chemistry of phenol-containing compounds.

    摘要翻译: 报道了一种新的多功能一类环状重氮二酰胺,通过Ene样反应有效和选择性地与苯酚和酪氨酸的侧链反应。 这种温和的水性酪氨酸连接反应在广泛的pH范围内起作用,并扩展了可用于小分子,肽和蛋白质修饰的水性化学成分。 显示酪氨酸连接反应与缓冲水溶液中天然酶和抗体的标记相容。 该反应为双特异性抗体提供了新的合成方法。 该反应将在肽和蛋白质化学和含酚化合物的化学中发现广泛的用途。

    Zinc finger binding domains for TNN
    5.
    发明授权
    Zinc finger binding domains for TNN 失效
    TNN的锌指结合结构域

    公开(公告)号:US07833784B2

    公开(公告)日:2010-11-16

    申请号:US11564141

    申请日:2006-11-28

    IPC分类号: C12N5/00 C12N15/00 C07H21/02

    CPC分类号: C12N9/50

    摘要: Polypeptides that contain zinc finger-nucleotide binding regions that bind to nucleotide sequences of the formula TNN are provided. Compositions containing a plurality of polypeptides, isolated heptapeptides possessing specific binding activity, polynucleotides that encode such polypeptides and methods of regulating gene expression with such polypeptides, compositions and polynucleotides are also provided.

    摘要翻译: 提供了含有结合式TNN的核苷酸序列的锌指核苷酸结合区的多肽。 还提供了含有多个多肽的组合物,具有特异性结合活性的分离的七肽,编码这些多肽的多核苷酸以及用这些多肽调节基因表达的方法,组合物和多核苷酸。

    Use of catalytic antibodies for synthesizing epothilone
    9.
    发明授权
    Use of catalytic antibodies for synthesizing epothilone 失效
    使用催化抗体合成埃坡霉素

    公开(公告)号:US06294374B1

    公开(公告)日:2001-09-25

    申请号:US09415453

    申请日:1999-10-08

    IPC分类号: C12S1300

    摘要: Three monoclonal aldolase antibodies, generated against a &bgr;-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions providing ent-9a-k by kinetic resolution. Compounds 9a, 9g and 9k were resolved in multi-gram quantities using 0.005-0.0004 mol % antibody catalyst. Enantiomerically pure starting materials, 9a-k, are useful synthons for the construction of epothilones A-E (2-6) and their analogs including 13-alkyl derivatives. Previously, the use of compound 9a as a synthon was reported in the preparation of epothilones A-D, 2-5. To further expand this synthon-based strategy, syntheses of epothilone E, 6, 13-methyl epothilone C, 7, and their trans-isomers have been achieved starting from enantiomerically pure thiazole aldols 9g and 9a, respectively, prepared by large-scale antibody catalyzed resolutions.

    摘要翻译: 通过反应性免疫针对β-二酮半抗原产生的三种单克隆醛缩酶抗体催化快速和高度对映选择性的醛缩醇反应,通过动力学拆分提供ent-9a-k。 化合物9a,9g和9k用0.005-0.0004mol%抗体催化剂以多克量分离。 对映体纯原料9a-k是构建埃坡霉素A-E(2-6)及其类似物包括13-烷基衍生物的有用合成物。 以前,在制备埃坡霉素A-D,2-5中报道了使用化合物9a作为合成子。 为了进一步扩展这种基于合成子的策略,从分别由大规模抗体制备的对映体纯的噻唑醛醇9g和9a开始合成埃坡霉素E,6,13-​​甲基埃博霉素C 7及其反式异构体 催化分解。