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    Preparation of polypeptides having an amide carboxyl terminal end
    4.
    发明授权
    Preparation of polypeptides having an amide carboxyl terminal end 失效
    制备具有酰胺羧基末端的多肽

    公开(公告)号：US5457033A

    公开(公告)日：1995-10-10

    申请号：US205816

    申请日：1994-03-04

    申请人： Joachim Engels ,  Wolfgang Konig ,  Hubert Mullner ,  Eugen Uhlmann ,  Waldemar Wetekam

    发明人： Joachim Engels ,  Wolfgang Konig ,  Hubert Mullner ,  Eugen Uhlmann ,  Waldemar Wetekam

    IPC分类号： C12N15/09 ,  C07H21/00 ,  C07H21/04 ,  C07K1/00 ,  C07K7/08 ,  C07K14/00 ,  C07K14/575 ,  C07K14/60 ,  C07K19/00 ,  C12N1/20 ,  C12N15/00 ,  C12N15/16 ,  C12N15/31 ,  C12P21/00 ,  C12P21/02 ,  C12R1/19 ,  C12N15/62 ,  C12N15/70 ,  C12P21/06

    CPC分类号： C07H21/00 ,  C07K14/60 ,  C12P21/02 ,  C07K2319/00 ,  C07K2319/75

    摘要： Polypeptides having a carboxamide carboxyl terminal end and a methionine residue, which is optionally bonded to a bacterial protein, on the amino end can be prepared by synthesis by genetic engineering methods of the corresponding polypeptide having at the C terminal end a glycine residue, and conversion of the latter enzymatically into the amino group of the desired carboxamide group. Peptides which have the aminoacid sequence of growth hormone releasing factor, part sequences thereof, or modifications of these peptides, are readily accessible by this means. The synthesis by genetic engineering methods is advantageously carried out via two gene fragments which are synthesized chemically from smaller, single-stranded structural units. The two gene fragments are then linked enzymatically to give the complete gene, which is incorporated into a suitable vector, amplified there, and the peptide is isolated directly or as a fused protein, and is converted enzymatically into the desired amide.

    摘要翻译： 具有羧酰胺羧基末端的多肽和任选地与细菌蛋白结合的氨基末端的甲硫氨酸残基可以通过在C末端具有甘氨酸残基的相应多肽的遗传工程方法合成，并且转化 后者酶促进入所需羧酰胺基团的氨基。 具有生长激素释放因子的氨基酸序列，其部分序列或这些肽的修饰的肽通过这种方式是容易获得的。 通过基因工程方法的合成有利地通过两个基因片段进行，这两个基因片段由较小的单链结构单元化学合成。 然后将两个基因片段酶促连接以产生完整的基因，其被并入合适的载体中，在那里扩增，并且肽直接或作为融合蛋白分离，并且被酶促转化为所需的酰胺。

    MODIFIED OLIGORIBONUCLEOTIDE ANALOGS WITH ENHANCED IMMUNOSTIMULATORY ACTIVITY
    5.
    发明申请
    MODIFIED OLIGORIBONUCLEOTIDE ANALOGS WITH ENHANCED IMMUNOSTIMULATORY ACTIVITY 审中-公开
    改良的寡核苷酸类似物与增强的免疫活性

    公开(公告)号：US20110244025A1

    公开(公告)日：2011-10-06

    申请号：US12946379

    申请日：2010-11-15

    申请人： Eugen Uhlmann ,  Arthur M. Krieg ,  Grayson B. Lipford

    发明人： Eugen Uhlmann ,  Arthur M. Krieg ,  Grayson B. Lipford

    IPC分类号： A61K9/127 ,  C07H21/02 ,  A61K39/00 ,  A61P11/00 ,  A61P31/14 ,  A61P35/00 ,  A61P37/08 ,  A61P37/04 ,  A61P11/06 ,  C12N5/02 ,  B82Y5/00

    CPC分类号： C07H21/00 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/3183 ,  C12N2310/321 ,  C12N2310/3515 ,  C12N2310/3529

    摘要： The invention provides immunostimulatory compositions and methods for their use. In particular, the immunostimulatory compositions of the invention include RNA-like polymers that incorporate an immunostimulatory sequence motif and at least one chemical modification to confer improved stability against nuclease degradation and improved activity. Specific modifications involving phosphate linkages, nucleotide analogs, and combinations thereof are provided. Compositions of the invention optionally include an antigen and can be used to stimulate an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an to allergic condition, or asthma. Modified oligoribonucleotide analogs of the invention are believed to stimulate Toll-like receptors TLR7 and TLR8.

    摘要翻译： 本发明提供免疫刺激组合物及其使用方法。 特别地，本发明的免疫刺激组合物包括纳入免疫刺激序列基序的RNA样聚合物和至少一种化学修饰，以提供改善的对核酸酶降解的稳定性和改善的活性。 提供了涉及磷酸键，核苷酸类似物及其组合的具体修饰。 本发明的组合物任选地包括抗原并且可以用于刺激免疫应答。 还提供了可用于治疗感染，癌症，过敏性疾病或哮喘的受试者的组合物和方法。 据信本发明的修饰的寡核糖核苷酸类似物刺激Toll样受体TLR7和TLR8。

    Polyamide nucleic acid derivatives and agents, and processes for preparing them
    9.
    发明授权
    Polyamide nucleic acid derivatives and agents, and processes for preparing them 失效
    聚酰胺核酸衍生物和试剂，及其制备方法

    公开(公告)号：US07550582B2

    公开(公告)日：2009-06-23

    申请号：US11855443

    申请日：2007-09-14

    申请人： Eugen Uhlmann ,  Gerhard Breipohl ,  David William Will

    发明人： Eugen Uhlmann ,  Gerhard Breipohl ,  David William Will

    IPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/68

    CPC分类号： C07K14/003 ,  A61K38/00 ,  Y10T436/143333

    摘要： The present invention relates to PNA derivatives which carry, at the C terminus, or at both the C and N termini of the PNA backbone, one or more phosphoryl radicals. The phosphoryl radicals carry, where appropriate, one or more labeling groups, groups for crosslinking, groups which promote intracellular uptake, or groups which increase the binding affinity of the PNA derivative for nucleic acids. The invention furthermore relates to a process for preparing the above-mentioned PNA derivatives and to their use as pharmaceuticals or diagnostic agents.

    摘要翻译： 本发明涉及在C末端或在PNA主链的C和N末端携带一个或多个磷酰基的PNA衍生物。 磷酰基在适当的情况下携带一个或多个标记基团，用于交联的基团，促进细胞内摄取的基团，或增加PNA衍生物对核酸的结合亲和力的基团。 本发明还涉及制备上述PNA衍生物的方法及其作为药物或诊断剂的用途。

    Polyamide-oligonucleotide derivatives, their preparation and use
    10.
    发明授权
    Polyamide-oligonucleotide derivatives, their preparation and use 失效
    聚酰胺 - 寡核苷酸衍生物，其制备和用途

    公开(公告)号：US07485421B2

    公开(公告)日：2009-02-03

    申请号：US10939214

    申请日：2004-09-10

    申请人： Eugen Uhlmann ,  Gerhard Breipohl

    发明人： Eugen Uhlmann ,  Gerhard Breipohl

    IPC分类号： C12Q1/68 ,  C07H21/04

    CPC分类号： C07H21/00 ,  A61K47/59 ,  A61K47/595 ,  A61K47/60 ,  A61K47/605 ,  C07K14/003

    摘要： Polyamide-oligonucleotide derivatives of the formula F[(DNA-Li)q(PNA-Li)r(DNA-Li)s(PNA)t]xF′ wherein q, r, s, t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s and t≧2; x is 1 to 20; DNA is a nucleic acid such as DNA or RNA or a known derivative thereof; Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O or S; PNA is a polyamide structure which contains at least one nucleotide base which is different from thymine; and F and F′ are end groups and/or are linked together by a covalent bond, and the physiologically tolerated salts thereof, a process for their preparation and their use as pharmaceutical, as gene probe and as primer, are described.

    摘要翻译： F [（DNA-Li）q（PNA-Li）r（DNA-Li）s（（N-1）） 其中q，r，s，t彼此独立地为0或1，其中总共为 两个或更多个相邻的q，r，s和t> = 2; x为1〜20; DNA是核酸如DNA或RNA或其已知衍生物; Li是DNA与PNA之间的共价连接，其中共价连接包含与C，N，O或S组成的系列中至少一个原子的键或有机基团; PNA是含有与胸腺嘧啶不同的至少一个核苷酸碱基的聚酰胺结构; 并且F和F'是端基和/或通过共价键连接在一起，并且描述了其生理学上耐受的盐，它们的制备方法及其作为药物的用途，作为基因探针和引物。