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公开(公告)号：US07217785B2
公开(公告)日：2007-05-15
申请号：US10142238
申请日：2002-05-08
申请人： John K. Bielicki
发明人： John K. Bielicki
CPC分类号： C07K14/775 , A61K38/00
摘要： The term “homology” or “homologous” means an amino acid similarity measured by the program, BLAST (Altschul et al (1997), “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs”, Nucleic Acids Res. 25:33 89–3402), and expressed as —(% identity n/n). In measuring homology between a peptide and a protein of greater size, homology is measured only in the corresponding region; that is, the protein is regarded as only having the same general length as the peptide, allowing for gaps and insertions.
摘要翻译： 术语“同源性”或“同源”是指程序BLAST（Altschul等（1997），“Gapped BLAST and PSI-BLAST：a new generation of protein database search programs”，Nucleic Acids Res。 25:33 89-3402），并表示为 - （同一性n / n）。 在测量更大尺寸的肽和蛋白质之间的同源性时，仅在相应的区域测量同源性; 也就是说，蛋白质被认为仅具有与肽相同的通用长度，允许间隙和插入。
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公开(公告)号：US20130123173A1
公开(公告)日：2013-05-16
申请号：US13643935
申请日：2011-04-28
申请人： John K. Bielicki , Jan Johansson
发明人： John K. Bielicki , Jan Johansson
CPC分类号： C07K14/001 , A61K38/00 , A61K38/16 , C07K14/00
摘要： The present invention provides non-naturally occurring polypeptides that are oxidation resistant and have cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABACI that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation; and diagnostic methods employing the peptides to evaluated cholesterol efflux activity.
摘要翻译： 本发明提供了抗天然存在的多肽，其具有与全长载脂蛋白（例如Apo AI和Apo E）相似的胆固醇流出活性，并且对于与全长载脂蛋白的ABACI平行的ABACI具有高选择性 。 本发明还提供包含这种多肽的组合物，鉴定，筛选和合成这些多肽的方法，治疗，预防或诊断与血脂异常，高胆固醇血症和炎症相关的疾病和病症的方法; 以及采用该肽评估胆固醇流出活性的诊断方法。
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公开(公告)号：US08415293B2
公开(公告)日：2013-04-09
申请号：US12999966
申请日：2009-06-17
申请人： John K. Bielicki , Jan Johansson
发明人： John K. Bielicki , Jan Johansson
摘要： The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.
摘要翻译： 本发明提供了一种非天然存在的多肽，其具有与全长载脂蛋白（例如Apo AI和Apo E）相似的胆固醇流出活性，并且对于与全长载脂蛋白的ABAC1平行的ABAC1具有高选择性。 本发明还提供包含这些多肽的组合物，鉴定，筛选和合成这些多肽的方法，以及治疗，预防或诊断与血脂异常，高胆固醇血症和炎症相关的疾病和病症的方法。
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公开(公告)号：US20100105619A1
公开(公告)日：2010-04-29
申请号：US12568501
申请日：2009-09-28
申请人： JOHN K. BIELICKI
发明人： JOHN K. BIELICKI
CPC分类号： C07K14/775 , A61K38/00
摘要： Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-IMilano (R173C) and apoA-IParis, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.
摘要翻译： 发现载脂蛋白（apo）A-IMilano（R173C）和apoA-IParis（R151C）所示的可交换载脂蛋白的两亲性α螺旋的半胱氨酸含量表现出对磷脂表面的有效的抗氧化活性。 在模拟HDL相关蛋白质的合成肽的两亲性α螺旋的疏水/亲水界面处添加游离巯基，对抑制脂质过氧化和保护磷脂免受水溶性自由基引发剂的这些肽赋予独特的抗氧化活性 。 这些肽可用作治疗心血管疾病，局部缺血，骨病和其它炎性相关疾病的治疗剂。
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公开(公告)号：US07691965B2
公开(公告)日：2010-04-06
申请号：US11014187
申请日：2004-12-15
CPC分类号： C07K14/775 , A61K38/00
摘要： The present invention provides peptides comprising at least one amphipathic alpha helix and having an cholesterol mediating activity and a ABCA stabilization activity. The invention further provides methods of using such peptides.
摘要翻译： 本发明提供了包含至少一种两亲性α螺旋并具有胆固醇介导活性和ABCA稳定活性的肽。 本发明还提供了使用这些肽的方法。
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公开(公告)号：US08987192B2
公开(公告)日：2015-03-24
申请号：US12519116
申请日：2007-12-13
申请人： John K. Bielicki , Jan Johansson
发明人： John K. Bielicki , Jan Johansson
IPC分类号： A61K38/00 , A61K38/16 , A61K45/00 , A61K47/24 , A61K49/00 , A61K51/00 , A61K9/127 , C07K14/00 , C07K14/47 , C07K14/705 , A61P3/06 , A61P9/00 , C07K14/775
CPC分类号： C07K14/775 , A61K38/00 , A61K38/16 , C07K14/4703
摘要： The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.
摘要翻译： 本发明提供了具有与全长载脂蛋白（例如Apo AI和Apo E）平行的胆固醇流出活性的非天然存在的多肽的家族，并且对于与全长载脂蛋白的ABAC1平行的ABAC1具有高选择性。 本发明还提供包含这些多肽的组合物，鉴定，筛选和合成这些多肽的方法，以及治疗，预防或诊断与血脂异常，高胆固醇血症和炎症相关的疾病和病症的方法。
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公开(公告)号：US20120329703A1
公开(公告)日：2012-12-27
申请号：US12519116
申请日：2007-12-13
申请人： John K. Bielicki , Jan Johansson
发明人： John K. Bielicki , Jan Johansson
CPC分类号： C07K14/775 , A61K38/00 , A61K38/16 , C07K14/4703
摘要： The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.
摘要翻译： 本发明提供了具有与全长载脂蛋白（例如Apo AI和Apo E）平行的胆固醇流出活性的非天然存在的多肽的家族，并且对于与全长载脂蛋白的ABAC1平行的ABAC1具有高选择性。 本发明还提供包含这些多肽的组合物，鉴定，筛选和合成这些多肽的方法，以及治疗，预防或诊断与血脂异常，高胆固醇血症和炎症相关的疾病和病症的方法。
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公开(公告)号：US07601802B2
公开(公告)日：2009-10-13
申请号：US11177225
申请日：2005-07-07
申请人： John K. Bielicki
发明人： John K. Bielicki
CPC分类号： C07K14/775 , A61K38/00
摘要： Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-IMilano (R173C) and apoA-IParis, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.
摘要翻译： 发现载脂蛋白（apo）A-IMilano（R173C）和apoA-IParis（R151C）所例示的可交换载脂蛋白的两亲性α螺旋的半胱氨酸含量表现出对磷脂表面的有效的抗氧化活性。 在模拟HDL相关蛋白质的合成肽的两亲性α螺旋的疏水/亲水界面处添加游离巯基，对抑制脂质过氧化和保护磷脂免受水溶性自由基引发剂的这些肽赋予独特的抗氧化活性 。 这些肽可用作治疗心血管疾病，局部缺血，骨病和其它炎性相关疾病的治疗剂。
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公开(公告)号：US07439323B2
公开(公告)日：2008-10-21
申请号：US11177237
申请日：2005-07-07
申请人： John K. Bielicki
发明人： John K. Bielicki
CPC分类号： C07K14/775 , A61K38/00
摘要： Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-IMilano (R173C) and apoA-IParis, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.
摘要翻译： 发现载脂蛋白（apo）AI Milano（R173C）和apoA-1巴黎（R151C）例证的可交换载脂蛋白的两亲性α螺旋的半胱氨酸含量显示出有效的 对磷脂表面的抗氧化活性。 在模拟HDL相关蛋白质的合成肽的两亲性α螺旋的疏水/亲水界面处添加游离巯基，对抑制脂质过氧化和保护磷脂免受水溶性自由基引发剂的这些肽赋予独特的抗氧化活性 。 这些肽可用作治疗心血管疾病，局部缺血，骨病和其它炎性相关疾病的治疗剂。
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公开(公告)号：US20110190196A1
公开(公告)日：2011-08-04
申请号：US12999966
申请日：2009-06-17
申请人： John K. Bielicki , Jan Johansson
发明人： John K. Bielicki , Jan Johansson
摘要： The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.
摘要翻译： 本发明提供了具有与全长载脂蛋白（例如Apo AI和Apo E）平行的胆固醇流出活性的非天然存在的多肽的家族，并且对于与全长载脂蛋白的ABAC1平行的ABAC1具有高选择性。 本发明还提供包含这些多肽的组合物，鉴定，筛选和合成这些多肽的方法，以及治疗，预防或诊断与血脂异常，高胆固醇血症和炎症相关的疾病和病症的方法。
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