利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

26 条记录 (耗时 0.046 秒)

    Animal model for helicobacter pylori infection
    1.
    发明授权
    Animal model for helicobacter pylori infection 失效
    幽门螺杆菌感染的动物模型

    公开(公告)号：US5625124A

    公开(公告)日：1997-04-29

    申请号：US273411

    申请日：1994-07-11

    申请人： Per Falk ,  Jeffrey I. Gordon

    发明人： Per Falk ,  Jeffrey I. Gordon

    IPC分类号： C12N9/10 ,  C12N15/85 ,  C12N5/00 ,  A61K49/00 ,  G01N33/567

    CPC分类号： C12N15/8509 ,  A01K67/0278 ,  C12N9/1051 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0337 ,  C12N2830/008

    摘要： Transgenic non-human animals are described which serve as a model for H. pylori infection of epithelial cells of the stomach and small intestine. The gut epithelial cells of the transgenic animals express one or more surface carbohydrate antigens which act as receptors for the bacterium H. pylori, a known causative agent of acid peptic disease, such as gastritis, stomach ulcers, duodenal ulcers, and strongly correlated with the development of gastric neoplasia. Methods for making and using the transgenic animals are also disclosed. The transgenic animals can be used to screen for compounds and conditions which block binding of H. pylori to the gut epithelium and/or ameliorate the H. pylori-associated pathogenesis of acid peptic disease and gastric adenocarcinoma.

    摘要翻译： 描述了作为幽门螺杆菌感染胃和小肠上皮细胞的模型的转基因非人动物。 转基因动物的肠上皮细胞表达一种或多种表面碳水化合物抗原，其作为细菌幽门螺杆菌的受体，幽门螺杆菌是酸消化性疾病的已知致病因子，例如胃炎，胃溃疡，十二指肠溃疡，并且与 发展胃肿瘤。 还公开了制备和使用转基因动物的方法。 转基因动物可用于筛选阻断幽门螺杆菌与肠上皮结合和/或改善幽门螺杆菌相关的酸性消化性疾病和胃腺癌发病机理的化合物和病症。

    Seryl-lysyl-based peptide and peptidomimetic inhibitors of N-myristoyl transferase as anti-infective agents
    3.
    发明授权
    Seryl-lysyl-based peptide and peptidomimetic inhibitors of N-myristoyl transferase as anti-infective agents 失效
    作为抗感染剂的N-肉豆蔻酰基转移酶的丝氨酰赖氨酰基肽和肽模拟抑制剂

    公开(公告)号：US06632921B1

    公开(公告)日：2003-10-14

    申请号：US09277573

    申请日：1999-03-26

    申请人： James A. Sikorski ,  Devadas Balekudru ,  Daniel P. Getman ,  David L. Brown ,  Srinivasan Nagarajan ,  Mark E. Zupec ,  Jeffrey I. Gordon

    发明人： James A. Sikorski ,  Devadas Balekudru ,  Daniel P. Getman ,  David L. Brown ,  Srinivasan Nagarajan ,  Mark E. Zupec ,  Jeffrey I. Gordon

    IPC分类号： C07K508

    CPC分类号： C07K5/06191 ,  A61K38/00 ,  C07K5/0606 ,  C07K5/081

    摘要： Seryl-lysyl-based peptide and peptidomimetic compounds are described as inhibitors of the enzyme N-myristoyl transferase to provide selective control of the fungal organism Candida albicans. Peptidomimetic compounds of particular interest are those of the formula: wherein R1 is selected form aminoalkyl, p-aminoalkylphenylalkyl, imidazolylalkylphenylalkyl, 2-alkylimidazolylalkylphenylalkyl, benzimidazolylalkylphenylalkyl and 2-alkylbenzimidazolylalkylphenylalkyl; wherein R2 is selected from hydrido, alkyl, cycloalkyl, akenyl, alkynyl, haloalkyl, benzyl, alkylphenylalkyl, alkoxyphenylalkyl, halophenylalkyl, phenethyl, cycloalkylalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, alkoxycycloalkylalkyl and naphthylalkyl; wherein Y is selected from carboxylic acid, hydroxamic acid, phosphonic acid and tetrazolyl; or a pharmaceutically-acceptable salt, amide or ester thereof. Compounds of the formula are species-specific inhibitors of C. albicans with little effect on human NMT enzyme and thus would.be useful in treating C. albicans fungal infections in humans.

    摘要翻译： 描述了基于丝氨酰赖氨酰的肽和拟肽化合物作为N-肉豆蔻酰转移酶酶的抑制剂，以提供对真菌生物体 的真菌生物的选择性控制。 特别感兴趣的拟肽化合物是下式的化合物：其中R 1选自氨基烷基，对氨基烷基苯基烷基，咪唑基烷基苯基烷基，2-烷基咪唑基烷基苯基烷基，苯并咪唑基烷基苯基烷基和2-烷基苯并咪唑基烷基苯基烷基; 其中R 1选自氢，烷基，环烷基，亚烯基，炔基，卤代烷基，苄基，烷基苯基烷基，烷氧基苯基烷基，卤代苯基烷基，苯乙基，环烷基烷基，卤代环烷基烷基，烷基环烷基烷基， 其中Y选自羧酸，异羟肟酸，膦酸和四唑基; 或其药学上可接受的盐，酰胺或酯。 式的化合物是 C的物种特异性抑制剂。 白色念珠菌 对人NMT酶几乎没有影响，因此可用于治疗 C。 白色念珠菌 人类真菌感染。

    Transgenic mouse model of prostate cancer
    4.
    发明授权
    Transgenic mouse model of prostate cancer 失效
    前列腺癌的转基因小鼠模型

    公开(公告)号：US5917124A

    公开(公告)日：1999-06-29

    申请号：US927986

    申请日：1997-09-12

    申请人： Jeffrey I. Gordon ,  Emily M. Garabedian

    发明人： Jeffrey I. Gordon ,  Emily M. Garabedian

    IPC分类号： A01K67/027 ,  C07K14/82 ,  C12N15/85 ,  A61F2/30

    CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K67/0278 ,  C07K14/82 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0331

    摘要： Disclosed are transgenic mice that produces prostate tumors and faithfully recapitulate many of the features of human prostatic carcinoma. It has been discovered that transcriptional regulatory elements active in Paneth cells, granule goblet cells, intermediate cells, or a combination, when used to express Simian Virus 40 large T antigen (TAg) in a transgenic mouse leads to development of prostate tumors in the mouse. The transcriptional regulatory elements are derived from the cryptdin-2 (CR2) gene. The disclosed mice develop prostatic intraepithelial neoplasia (PIN) at an early age. Progression with local invasion, loss of androgen-dependence and eventual metastases are hallmarks of the disclosed transgenic mice. Preferred embodiments of the disclosed transgenic mice have several important characteristics: (1) the disease is fully penetrant--all mice containing the SV40 TAg transgene develop prostatic cancer; (2) the first appearance of SV40 TAg always coincides with the appearance of cellular atypia in prostatic acini; (3) the rate of progression of the neoplasia is rapid; (4) prostatic adenocarcinomas in the transgenic mice exhibit foci of neuroendocrine differentiation; (5) metastatic lesions are common in the lymph nodes, liver, lung, and bone of the disclosed transgenic mice and are evident early in life; and (6) the lifespan of the disclosed transgenic animals is not shortened by transgene-related pathology in other organs--female transgenic mice develop normally and have a normal lifespan.

    摘要翻译： 公开了产生前列腺肿瘤并忠实地重现人类前列腺癌的许多特征的转基因小鼠。 已经发现，当用于在转基因小鼠中表达猿猴病毒40大T抗原（TAg）时，在Paneth细胞，颗粒状杯状细胞，中间细胞或组合中活跃的转录调节元件导致小鼠中前列腺肿瘤的发展 。 转录调节元件衍生自cryptdin-2（CR2）基因。 所公开的小鼠在早期发展为前列腺上皮内瘤变（PIN）。 本地入侵，丧失雄激素依赖性和最终转移的进展是所公开的转基因小鼠的标志。 所公开的转基因小鼠的优选实施方案具有几个重要特征：（1）该疾病是完全渗透的，所有含有SV40TT转基因的小鼠均发展为前列腺癌; （2）SV40的首次出现TAg始终与前列腺炎的细胞异型现象相吻合; （3）瘤形成进展迅速; （4）前列腺腺癌转基因小鼠表现出神经内分泌分化的病灶; （5）转移性病变在所公开的转基因小鼠的淋巴结，肝，肺和骨中是常见的，并且在生命早期是明显的; 和（6）所公开的转基因动物的寿命不会因其他器官中的转基因相关病理学而缩短 - 雌性转基因小鼠正常发育并具有正常的寿命。

    Method for protein N-myristoylation
    5.
    发明授权
    Method for protein N-myristoylation 失效
    蛋白质N-肉豆蔻酰化方法

    公开(公告)号：US5436138A

    公开(公告)日：1995-07-25

    申请号：US90383

    申请日：1993-07-12

    申请人： Robert J. Duronio ,  Peter O. Olins ,  Jeffrey I. Gordon

    发明人： Robert J. Duronio ,  Peter O. Olins ,  Jeffrey I. Gordon

    IPC分类号： C12N15/09 ,  C12N9/10 ,  C12N9/12 ,  C12N15/54 ,  C12P21/00 ,  C12R1/19 ,  C12N15/63 ,  C12N15/70

    CPC分类号： C12N9/1029 ,  C12N9/12

    摘要： There is disclosed a method for providing for the coexpression of N-myristoyltransferase and a protein substrate for said N-myristoyltransferase in E. coli comprising introducing into E. coli a dual plasmid system comprising (A) the isopropyl-.beta.-D-thiogalactopyranoside-inducible tac promoter, the g10-L ribosome binding site, a NMT gene, the kanamycin resistance gene and the p15A origin of replication in operable sequence and (B) the recA promoter, the g10-L ribosome binding site, a mammalian gene, the ampicillin resistance gene and the Col E1 origin of replication in operable sequence. This allows production of mammalian N-myristoylproteins or proteins containing covalently linked analogs of myristate with altered physical-chemical properties.

    摘要翻译： 公开了一种用于在大肠杆菌中提供N-肉豆蔻酰转移酶和所述N-肉豆蔻酰转移酶的蛋白质底物的方法，其包括将包含（A）异丙基-β-D-硫代半乳糖苷 - 可诱导的tac启动子，g10-L核糖体结合位点，NMT基因，卡那霉素抗性基因和p15A复制起点的可操作的序列和（B）recA启动子，g10-L核糖体结合位点，哺乳动物基因， 氨苄青霉素抗性基因和Col E1复制起点。 这允许产生哺乳动物N-肉豆蔻酰蛋白或含有具有改变的物理化学性质的肉豆蔻酸的共价连接类似物的蛋白质。

    Seryl-lysyl-based peptide and peptidomimetic inhibitors of N-myristoyl transferase as anti-infective agents
    10.
    发明授权
    Seryl-lysyl-based peptide and peptidomimetic inhibitors of N-myristoyl transferase as anti-infective agents 失效
    作为抗感染剂的N-肉豆蔻酰基转移酶的丝氨酰赖氨酰基肽和肽模拟抑制剂

    公开(公告)号：US5942600A

    公开(公告)日：1999-08-24

    申请号：US823101

    申请日：1997-03-24

    申请人： James A. Sikorski ,  Balekudru Devadas ,  Daniel P. Getman ,  David L. Brown ,  Srinivasan Nagarajan ,  Mark E. Zupec ,  Jeffrey I. Gordon

    发明人： James A. Sikorski ,  Balekudru Devadas ,  Daniel P. Getman ,  David L. Brown ,  Srinivasan Nagarajan ,  Mark E. Zupec ,  Jeffrey I. Gordon

    IPC分类号： A61K38/00 ,  C07K5/06 ,  C07K5/083 ,  A61K38/06

    CPC分类号： C07K5/06191 ,  C07K5/0606 ,  C07K5/081 ,  A61K38/00

    摘要： Seryl-lysyl-based peptide and peptidomimetic compounds are described as inhibitors of the enzyme N-myristoyl transferase to provide selective control of the fungal organism Candida albicans. Peptidomimetic compounds of particular interest are those of the formula: ##STR1## wherein R.sup.1 is selected form aminoalkyl, p-aminoalkylphenylalkyl, imidazolylalkylphenylalkyl, 2-alkylimidazolylalkylphenylalkyl, benzimidazolylalkylphenylalkyl and 2-alkylbenzimidazolylalkylphenylalkyl; wherein R.sup.2 is selected from hydrido, alkyl, cycloalkyl, akenyl, alkynyl, haloalkyl, benzyl, alkylphenylalkyl, alkoxyphenylalkyl, halophenylalkyl, phenethyl, cycloalkylalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, alkoxycycloalkylalkyl and naphthylalkyl; wherein Y is selected from carboxylic acid, hydroxamic acid, phosphonic acid and tetrazolyl; or a pharmaceutically-acceptable salt, amide or ester thereof. Compounds of the formula are species-specific inhibitors of C. albicans with little effect on human NMT enzyme and thus would be useful in treating C. albicans fungal infections in humans.

    摘要翻译： 基于丝氨酰赖氨酰的肽和拟肽化合物被描述为N-肉豆蔻酰转移酶的抑制剂，以提供真菌生物体白色念珠菌的选择性控制。 特别感兴趣的拟肽化合物是下式的化合物：其中R1选自氨基烷基，对氨基烷基苯基烷基，咪唑基烷基苯基烷基，2-烷基咪唑基烷基苯基烷基，苯并咪唑基烷基苯基烷基和2-烷基苯并咪唑基烷基苯基烷基; 烷基，环烷基，烯基，炔基，卤代烷基，苄基，烷基苯基烷基，烷氧基苯基烷基，卤代苯基烷基，苯乙基，环烷基烷基，卤代环烷基烷基，烷基环烷基烷基，烷氧基环烷基烷基和萘基烷基。 其中Y选自羧酸，异羟肟酸，膦酸和四唑基; 或其药学上可接受的盐，酰胺或酯。 式的化合物是白色念珠菌的物种特异性抑制剂，对人NMT酶几乎没有影响，因此可用于治疗人类白色念珠菌真菌感染。