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    Isolated GRP94 ligand binding domain polypeptide and nucleic acid encoding same, and screening methods employing same
    1.
    发明申请
    Isolated GRP94 ligand binding domain polypeptide and nucleic acid encoding same, and screening methods employing same 审中-公开
    分离的GRP94配体结合域多肽和编码相同的核酸，以及使用其的筛选方法

    公开(公告)号：US20080160636A1

    公开(公告)日：2008-07-03

    申请号：US11821459

    申请日：2007-06-22

    Applicant: Daniel T. Gewirth ,  Christopher V. Nicchitta

    Inventor： Daniel T. Gewirth ,  Christopher V. Nicchitta

    IPC: G01N33/566 ,  C07K14/00 ,  C07K16/18

    CPC classification number: C07K14/47 ,  A61K38/00 ,  C07K2319/00 ,  G01N2500/00

    Abstract: An isolated GRP94 ligand binding domain polypeptide. In some embodiments, the isolated GRP94 ligand binding domain polypeptide includes (a) an amino acid sequence encoded by a nucleic acid molecule that includes a nucleotide sequence selected from among: (i) nucleotides 310-1116 of SEQ ID NO: 1; (ii) nucleotides 142-948 of SEQ ID NO: 3; (iii) nucleotides 142-948 of SEQ ID NO: 5; and (iv) an amino acid sequence encoded by a nucleotide sequence at least 95% identical to any of (i)-(iii); (b) an amino acid sequence selected from among (v) amino acids 69-337 of SEQ ID NO: 2; (vi) amino acids 48-316 of SEQ ID NO: 4; (vii) amino acids 48-316 of SEQ ID NO: 6; and (viii) an amino acid sequence at least 95% identical to any of (iv)-(vi); or (c) an amino acid sequence that is immunologically cross-reactive with an antibody that specifically binds to a polypeptide consisting of an amino acid sequence as set forth in any one of (a) and (b), wherein the GRP94 ligand binding domain (LBD) polypeptide binds a GRP94 ligand selected from the group consisting of 4,4′-dianilino-1,1-binaphthyl-5,5-disulfonic acid (bis-ANS) and N-ethylcarboxamidoadenosine (NECA). Also disclosed are isolated polynucleotides encoding the disclosed polypeptides and methods of using the same to identify modulators of Hsp90 proteins.

    Abstract translation: 分离的GRP94配体结合域多肽。 在一些实施方案中，分离的GRP94配体结合结构域多肽包括（a）由核酸分子编码的氨基酸序列，其包含选自以下的核苷酸序列：（i）SEQ ID NO：1的核苷酸310-1116; （ii）SEQ ID NO：3的核苷酸142-948; （iii）SEQ ID NO：5的核苷酸142-948; 和（iv）由与（i） - （iii）中任一个至少95％相同的核苷酸序列编码的氨基酸序列; （b）选自（v）SEQ ID NO：2的（v）氨基酸69-337的氨基酸序列; （vi）SEQ ID NO：4的氨基酸48-316; （vii）SEQ ID NO：6的氨基酸48-316; 和（viii）与（iv） - （vi）中任何一个至少95％相同的氨基酸序列; 或（c）与特异性结合由（a）和（b）中任一项所述的氨基酸序列组成的多肽的抗体具有免疫交叉反应性的氨基酸序列，其中所述GRP94配体结合域 （LBD）多肽结合选自4,4'-二氨基-1,1'-联萘-5,5-二磺酸（bis-ANS）和N-乙基甲酰胺基腺苷（NECA）的GRP94配体。 还公开了编码所公开的多肽的分离的多核苷酸及其使用以鉴定Hsp90蛋白的调节剂的方法。

    Isolated GRP94 ligand binding domain polypeptide and nucleic acid encoding same, and screening methods employing same
    5.
    发明授权
    Isolated GRP94 ligand binding domain polypeptide and nucleic acid encoding same, and screening methods employing same 失效
    分离的GRP94配体结合域多肽和编码相同的核酸，以及使用其的筛选方法

    公开(公告)号：US07235649B2

    公开(公告)日：2007-06-26

    申请号：US09968436

    申请日：2001-10-01

    Applicant: Daniel T. Gewirth ,  Christopher V. Nicchitta

    Inventor： Daniel T. Gewirth ,  Christopher V. Nicchitta

    IPC: C07H21/02 ,  C07H21/04 ,  A61K38/00

    CPC classification number: C07K14/47 ,  A61K38/00 ,  C07K2319/00 ,  G01N2500/00

    Abstract: We claim an isolated nucleic acid molecule encoding a ligand binding domain of glucose regulated protein of 94 kDa (GRP94), a chimeric polynucleotide consisting of said nucleic acid molecule operably linked to a heterologous promoter wherein said nucleic acid molecule is optionally linked to a polynucleotide encoding a heterologous polypeptide so as to form a fusion protein between the GRP94 ligand binding domain polypeptide and said heterologous polypeptide, a vector consisting of said chimeric polynucleotide, and a host cell comprising said chimeric polynucleotide.

    Abstract translation: 我们要求一种分离的核酸分子，其编码94kDa的葡萄糖调节蛋白（GRP94）的配体结合结构域，该嵌合多核苷酸由与异源启动子可操作地连接的所述核酸分子组成，其中所述核酸分子任选与多核苷酸编码 异源多肽，以在GRP94配体结合结构域多肽和所述异源多肽之间形成融合蛋白，由所述嵌合多核苷酸组成的载体和包含所述嵌合多核苷酸的宿主细胞。

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