公开(公告)号：US20100221264A1

公开(公告)日：2010-09-02

申请号：US12498157

申请日：2009-07-06

申请人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

发明人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

IPC分类号： A61K39/395 ,  A61K31/655 ,  A61K38/16 ,  A61P31/18 ,  A61K31/56

CPC分类号： A61K45/06 ,  A61K31/56 ,  C07K14/005 ,  C12N2740/16043 ,  C12N2740/16222 ,  G01N2333/161 ,  A61K2300/00

摘要： Inhibition of HIV-1 replication by disrupting the processing of the viral Gag capsid (CA) protein (p24) from the CA-spacer peptide 1 (SP1) protein precursor (p25) is disclosed. Amino acid sequences containing a mutation in the Gag p25 protein, with the mutation resulting in a decrease in the inhibition of processing of p25 to p24 by dimethylsuccinyl betulinic acid or dimethylsuccinyl betulin, polynucleotides encoding such mutated sequences and antibodies that selectively bind such mutated sequences are also included. Methods of inhibiting, inhibitory compounds and methods of discovering inhibitory compounds that target proteolytic processing of the HIV Gag protein are included. In one embodiment, such compounds inhibit the interaction of the HIV protease enzyme with Gag by binding to the Gag proteolytic cleavage site rather than to the protease enzyme. In another embodiment, viruses or recombinant proteins that contain mutations in the region of the Gag proteolytic cleavage site can be used in screening assays to identify compounds that target proteolytic processing.

摘要翻译： 公开了通过破坏来自CA-间隔肽1（SP1）蛋白前体（p25）的病毒Gag衣壳（CA）蛋白（p24））的加工来抑制HIV-1复制。 含有Gag p25蛋白突变的氨基酸序列，突变导致二甲基琥珀酰桦树酸或二甲基琥珀酰基桦木醇处理p25至p24的抑制作用降低，编码这种突变序列的多核苷酸和选择性结合这种突变序列的抗体是 也包括在内。 包括抑制，抑制化合物的方法和发现靶向HIV Gag蛋白的蛋白水解加工的抑制性化合物的方法。 在一个实施方案中，这样的化合物通过结合Gag蛋白水解切割位点而不是蛋白酶抑制HIV蛋白酶与Gag的相互作用。 在另一个实施方案中，在Gag蛋白水解切割位点区域中含有突变的病毒或重组蛋白质可用于筛选测定以鉴定靶向蛋白水解加工的化合物。

公开(公告)号：US20080233559A1

公开(公告)日：2008-09-25

申请号：US11962315

申请日：2007-12-21

申请人： Karl SALZWEDEL ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

发明人： Karl SALZWEDEL ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

IPC分类号： C12Q1/70

CPC分类号： A61K31/215 ,  A61K31/56 ,  A61K31/567 ,  A61K45/06 ,  C07K14/005 ,  C12N2740/16043 ,  C12N2740/16222 ,  G01N33/56988 ,  G01N2333/161 ,  A61K2300/00

摘要： Inhibition of HIV-1 replication by disrupting the processing of the viral Gag capsid (CA) protein (p24) from the CA-spacer peptide 1 (SP1) protein precursor (p25) is disclosed. Amino acid sequences containing a mutation in the Gag p25 protein, with the mutation resulting in a decrease in the inhibition of processing of p25 to p24 by dimethylsuccinyl betulinic acid or dimethylsuccinyl betulin, polynucleotides encoding such mutated sequences and antibodies that selectively bind such mutated sequences are also included. Methods of inhibiting, inhibitory compounds and methods of discovering inhibitory compounds that target proteolytic processing of the HIV Gag protein are included. In one embodiment, such compounds inhibit the interaction of the HIV protease enzyme with Gag by binding to Gag rather than to the protease enzyme. In another embodiment, viruses or recombinant proteins that contain mutations in the region of the Gag proteolytic cleavage site can be used in screening assays to identify compounds that target proteolytic processing.

摘要翻译： 公开了通过破坏来自CA-间隔肽1（SP1）蛋白前体（p25）的病毒Gag衣壳（CA）蛋白（p24））的加工来抑制HIV-1复制。 含有Gag p25蛋白突变的氨基酸序列，突变导致二甲基琥珀酰桦树酸或二甲基琥珀酰基桦木醇处理p25至p24的抑制作用降低，编码这种突变序列的多核苷酸和选择性结合这种突变序列的抗体是 也包括在内。 包括抑制，抑制化合物的方法和发现靶向HIV Gag蛋白的蛋白水解加工的抑制性化合物的方法。 在一个实施方案中，这些化合物通过结合Gag而不是蛋白酶抑制HIV蛋白酶与Gag的相互作用。 在另一个实施方案中，在Gag蛋白水解切割位点区域中含有突变的病毒或重组蛋白质可用于筛选测定以鉴定靶向蛋白水解加工的化合物。

公开(公告)号：US08318425B2

公开(公告)日：2012-11-27

申请号：US12498157

申请日：2009-07-06

申请人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

发明人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

IPC分类号： C12Q1/70 ,  C12Q1/68 ,  A01N61/00 ,  A01N57/00 ,  A61K31/00 ,  A61K31/66

CPC分类号： A61K45/06 ,  A61K31/56 ,  C07K14/005 ,  C12N2740/16043 ,  C12N2740/16222 ,  G01N2333/161 ,  A61K2300/00

摘要： Inhibition of HIV-1 replication by disrupting the processing of the viral Gag capsid (CA) protein (p24) from the CA-spacer peptide 1 (SP1) protein precursor (p25) is disclosed. Amino acid sequences containing a mutation in the Gag p25 protein, with the mutation resulting in a decrease in the inhibition of processing of p25 to p24 by dimethylsuccinyl betulinic acid or dimethylsuccinyl betulin, polynucleotides encoding such mutated sequences and antibodies that selectively bind such mutated sequences are also included. Methods of inhibiting, inhibitory compounds and methods of discovering inhibitory compounds that target proteolytic processing of the HIV Gag protein are included. In one embodiment, such compounds inhibit the interaction of the HIV protease enzyme with Gag by binding to the Gag proteolytic cleavage site rather than to the protease enzyme. In another embodiment, viruses or recombinant proteins that contain mutations in the region of the Gag proteolytic cleavage site can be used in screening assays to identify compounds that target proteolytic processing.

摘要翻译： 公开了通过破坏来自CA-间隔肽1（SP1）蛋白前体（p25）的病毒Gag衣壳（CA）蛋白（p24））的加工来抑制HIV-1复制。 含有Gag p25蛋白突变的氨基酸序列，突变导致二甲基琥珀酰桦树酸或二甲基琥珀酰基桦木醇处理p25至p24的抑制作用降低，编码这种突变序列的多核苷酸和选择性结合这种突变序列的抗体是 也包括在内。 包括抑制，抑制化合物的方法和发现靶向HIV Gag蛋白的蛋白水解加工的抑制性化合物的方法。 在一个实施方案中，这样的化合物通过结合Gag蛋白水解切割位点而不是蛋白酶抑制HIV蛋白酶与Gag的相互作用。 在另一个实施方案中，在Gag蛋白水解切割位点区域中含有突变的病毒或重组蛋白质可用于筛选测定以鉴定靶向蛋白水解加工的化合物。

公开(公告)号：US07537765B2

公开(公告)日：2009-05-26

申请号：US10851637

申请日：2004-05-24

申请人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

发明人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

IPC分类号： A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K38/00

CPC分类号： A61K31/215 ,  A61K31/56 ,  A61K31/567 ,  A61K45/06 ,  C07K14/005 ,  C12N2740/16043 ,  C12N2740/16222 ,  G01N33/56988 ,  G01N2333/161 ,  A61K2300/00

摘要： Inhibition of HIV-1 replication by disrupting the processing of the viral Gag capsid (CA) protein (p24) from the CA-spacer peptide 1 (SP1) protein precursor (p25) is disclosed. Amino acid sequences containing a mutation in the Gag p25 protein, with the mutation resulting in a decrease in the inhibition of processing of p25 to p24 by dimethylsuccinyl betulinic acid or dimethylsuccinyl betulin, polynucleotides encoding such mutated sequences and antibodies that selectively bind such mutated sequences are also included. Methods of inhibiting, inhibitory compounds and methods of discovering inhibitory compounds that target proteolytic processing of the HIV Gag protein are included. In one embodiment, such compounds inhibit the interaction of the HIV protease enzyme with Gag by binding to Gag rather than to the protease enzyme. In another embodiment, viruses or recombinant proteins that contain mutations in the region of the Gag proteolytic cleavage site can be used in screening assays to identify compounds that target proteolytic processing.

摘要翻译： 公开了通过破坏来自CA-间隔肽1（SP1）蛋白前体（p25）的病毒Gag衣壳（CA）蛋白（p24））的加工来抑制HIV-1复制。 含有Gag p25蛋白突变的氨基酸序列，突变导致二甲基琥珀酰桦树酸或二甲基琥珀酰基桦木醇处理p25至p24的抑制作用降低，编码这种突变序列的多核苷酸和选择性结合这种突变序列的抗体是 也包括在内。 包括抑制，抑制化合物的方法和发现靶向HIV Gag蛋白的蛋白水解加工的抑制性化合物的方法。 在一个实施方案中，这些化合物通过结合Gag而不是蛋白酶抑制HIV蛋白酶与Gag的相互作用。 在另一个实施方案中，在Gag蛋白水解切割位点区域中含有突变的病毒或重组蛋白质可用于筛选测定以鉴定靶向蛋白水解加工的化合物。

公开(公告)号：US20080200550A1

公开(公告)日：2008-08-21

申请号：US11597431

申请日：2005-05-24

申请人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

发明人： Karl Salzwedel ,  Feng Li ,  Carl T. Wild ,  Graham P. Allaway ,  Eric O. Freed

IPC分类号： A61K31/557

CPC分类号： A61K31/215 ,  A61K31/56 ,  A61K31/567 ,  A61K45/06 ,  C07K14/005 ,  C12N2740/16043 ,  C12N2740/16222 ,  G01N33/56988 ,  G01N2333/161 ,  A61K2300/00

摘要： Inhibition of HIV-1 replication by disrupting the processing of the viral Gag capsid (CA) protein (p24) from the CA-spacer peptide 1 (SP1) protein precursor (p25) is disclosed. Amino acid sequences containing a mutation in the Gag p25 protein, with the mutation resulting in a decrease in the inhibition of processing of p25 to p24 by dimethylsuccinyl betulinic acid or dimethylsuccinyl betulin, polynucleotides encoding such mutated sequences and antibodies that selectively bind such mutated sequences are also included. Methods of inhibiting, inhibitory compounds and methods of discovering inhibitory compounds that target proteolytic processing of the HIV Gag protein are included. In one embodiment, such compounds inhibit the interaction of the HIV protease enzyme with Gag by binding to Gag rather than to the protease enzyme. In another embodiment, viruses or recombinant proteins that contain mutations in the region of the Gag proteolytic cleavage site can be used in screening assays to identify compounds that target proteolytic processing.

摘要翻译： 公开了通过破坏来自CA-间隔肽1（SP1）蛋白前体（p25）的病毒Gag衣壳（CA）蛋白（p24））的加工来抑制HIV-1复制。 含有Gag p25蛋白突变的氨基酸序列，突变导致二甲基琥珀酰桦树酸或二甲基琥珀酰基桦木醇处理p25至p24的抑制作用降低，编码这种突变序列的多核苷酸和选择性结合这种突变序列的抗体是 也包括在内。 包括抑制，抑制化合物的方法和发现靶向HIV Gag蛋白的蛋白水解加工的抑制性化合物的方法。 在一个实施方案中，这些化合物通过结合Gag而不是蛋白酶抑制HIV蛋白酶与Gag的相互作用。 在另一个实施方案中，在Gag蛋白水解切割位点区域中含有突变的病毒或重组蛋白质可用于筛选测定以鉴定靶向蛋白水解加工的化合物。