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    Preventing endogenous aminopeptidase mediated n-terminal amino acid cleavage during expression of foreign genes in bacteria
    1.
    发明授权
    Preventing endogenous aminopeptidase mediated n-terminal amino acid cleavage during expression of foreign genes in bacteria 失效
    在细菌中外源基因表达期间防止内源性氨基肽酶介导的n末端氨基酸切割

    公开(公告)号：US6165746A

    公开(公告)日：2000-12-26

    申请号：US446667

    申请日：1995-05-26

    申请人： Markus Heitzmann ,  Rao Movva ,  Paul Ramage

    发明人： Markus Heitzmann ,  Rao Movva ,  Paul Ramage

    IPC分类号： C12N15/09 ,  C07K14/52 ,  C07K14/54 ,  C12N15/10 ,  C12P21/02 ,  C12P21/06 ,  C12R1/19

    CPC分类号： C12N15/10 ,  C07K14/54 ,  C07K14/5412 ,  C12P21/06

    摘要： A process for the recombinant preparation in a bacterial host of the mature form of a mammalian protein or peptide of formula X-Pro-Z, which is subject to processing by endogenous bacterial aminopeptidases is provided. In the formula X-Pro-Z, X is a single N-terminal amino acid other than proline, and Z is the remaining sequence of amino acid residues of the protein or peptide. The process comprises inserting into a cell of the bacterial host an appropriate vector containing DNA coding for Met-Y-X-Pro-Z, in which Y is a natural amino acid that is specifically cleavable in vitro from X-Pro-Z by an aminopeptidases and that imparts resistance to in vivo processing by endogenous bacterial aminopeptidases. The cell is then induced to express the expression product Met-Y-X-Pro-Z which is then treated with an appropriate aminopeptidase to cleave off Met and Y.

    摘要翻译： PCT No.PCT / EP93 / 03349 Sec。 371日期：1995年5月26日 102（e）日期1995年5月26日PCT提交1993年11月29日PCT公布。 公开号WO94 / 12659 日期1994年6月9日提供了在内源性细菌氨基肽酶处理的哺乳动物蛋白质或式X-Pro-Z肽的成熟形式的细菌宿主中的重组制备方法。 在式X-Pro-Z中，X是脯氨酸以外的单个N-末端氨基酸，Z是蛋白质或肽的氨基酸残基的剩余序列。 该方法包括将含有编码Met-YX-Pro-Z的DNA的合适载体插入到细菌宿主的细胞中，其中Y是天然氨基酸，其在体外可通过氨基肽酶从X-Pro-Z中切割， 其赋予内源性细菌氨基肽酶对体内加工的抵抗力。 然后诱导细胞表达表达产物Met-Y-X-Pro-Z，然后用合适的氨基肽酶处理以切割Met和Y.

    PEPTIDES
    3.
    发明申请
    PEPTIDES 审中-公开

    公开(公告)号：US20080318838A1

    公开(公告)日：2008-12-25

    申请号：US12169134

    申请日：2008-07-08

    申请人： Wilfried Bauer ,  Robin Breckenridge ,  Francois Cardinaux ,  Frank Gombert ,  Hermann Gram ,  Paul Ramage ,  Helmut Schneider ,  Rudolf Waelchli ,  Rainer Albert ,  Ian Lewis

    发明人： Wilfried Bauer ,  Robin Breckenridge ,  Francois Cardinaux ,  Frank Gombert ,  Hermann Gram ,  Paul Ramage ,  Helmut Schneider ,  Rudolf Waelchli ,  Rainer Albert ,  Ian Lewis

    IPC分类号： A61K38/00 ,  C07K7/00 ,  C12P21/04 ,  C12N15/11 ,  A61P19/00 ,  C12N15/00 ,  C12N1/20

    CPC分类号： C07K14/005 ,  A61K38/00 ,  C07K14/635 ,  C07K2319/00 ,  C07K2319/50 ,  C07K2319/75 ,  C12N2795/10222

    摘要： PTH compounds having PTH-like activity and comprising at least one modification, said modification being either 1. at least one radical selected from a L- or D-α-amino acid, C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to the terminal amino group of the PTH compound, and/or at least one radical selected from C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to one or more side chain amino groups of the PTH compound, or 2. at least one α-amino acid unit in the positions 1 to 38 of a naturally occurring PTH sequence being replaced by a natural or unnatural amino acid unit optionally in protected form, whereby the α-amino acid units present in positions 1 and 2 at the amino terminus of the PTH sequence may be replaced by a pseudo-peptide, or a combination of such modifications, in free form or in salt form, have pharmacological activity, e.g. for preventing or treating all bone conditions which are associated with increased calcium depletion or resorption or in which calcium fixation in the bone is desirable.

    摘要翻译： 具有PTH样活性并且包含至少一个修饰的PTH化合物，所述修饰是1.至少一个选自L-或D-α-氨基酸，C2-6羰基和任选取代的C 1-8烷基的基团，C 2-8烯基 ，C 2-8炔基，芳烷基，芳烯基或C 3-6环烷基-C 1-4烷基，并且连接到PTH化合物的末端氨基，和/或至少一个选自C 2-6烷氧基羰基和任选取代的C 1-8烷基基团，C 2-8烯基 ，C 2-8炔基，芳烷基，芳烯基或C 3-6环烷基-C 1-4烷基，并且连接到PTH化合物的一个或多个侧链氨基，或2个至少一个α-氨基酸单元的位置1至38 天然存在的PTH序列被任选以保护形式的天然或非天然氨基酸单元替代，由此存在于PTH序列的氨基末端的位置1和2中的α-氨基酸单元可被假肽替代，或 这些修改的组合，免费的 m或盐形式，具有药理活性，例如。 用于预防或治疗与增加的钙耗竭或吸收相关的所有骨骼状况或其中期望骨中的钙固定。

    X-Ray Structure of Human Fpps and Use For Selecting Fpps Binding Compounds
    4.
    发明申请
    X-Ray Structure of Human Fpps and Use For Selecting Fpps Binding Compounds 审中-公开
    人类Fpps的X射线结构和用于选择Fpps结合化合物的用途

    公开(公告)号：US20080139449A1

    公开(公告)日：2008-06-12

    申请号：US11722574

    申请日：2006-01-02

    申请人： Wolfgang Jahnke ,  Jean-Michel Rondeau ,  Martin Geiser ,  Paul Ramage ,  Andre Strauss

    发明人： Wolfgang Jahnke ,  Jean-Michel Rondeau ,  Martin Geiser ,  Paul Ramage ,  Andre Strauss

    IPC分类号： A61K38/00 ,  C12N9/10 ,  C12P21/04 ,  A61P43/00 ,  C12Q1/00 ,  G06G7/48

    CPC分类号： C12N9/1085 ,  C07K2299/00

    摘要： The present invention relates to crystalline human farnesyl diphosphate synthase (FPPS), to the three-dimensional structure of free FPPS as well as the three-dimensional structures of FPPS in complex with substrates such as IPP (isopentenyl diphosphate) and/or with inhibitors such as Zometa® or Aredia®. Further, methods for preparing crystals of human FPPS are described. According to the invention the crystals can be used to determine the structures of FPPS homologs mutants, complexes with ligands, FPPS crystal forms and similar molecules of unknown structure. The invention further relates to the use of FPPS crystals to select new FPPS ligands, e.g. by X-ray screening and to design and/or identify inhibitors against FPPS. Furthermore, the invention relates to NMR methods for selecting and/or identifying new low molecular weight binders to FPPS, which represent new therapeutic agents.

    摘要翻译： 本发明涉及结晶人类法呢基二磷酸合成酶（FPPS），与游离FPPS的三维结构以及FPPS与底物复合物（例如IPP（异戊烯二磷酸酯））和/或与抑制剂的复合物的三维结构 作为Zometa或Aredia（R）。 此外，描述了制备人FPPS晶体的方法。 根据本发明，晶体可用于确定FPPS同系物突变体，配体配合物，FPPS晶体形式和未知结构的类似分子的结构。 本发明还涉及使用FPPS晶体来选择新的FPPS配体，例如， 通过X射线检查和设计和/或识别针对FPPS的抑制剂。 此外，本发明涉及用于选择和/或鉴定新的FPPS的低分子量粘合剂的NMR方法，其代表新的治疗剂。