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公开(公告)号：US20080287311A1
公开(公告)日：2008-11-20
申请号：US11996496
申请日：2006-07-24
CPC分类号： C12N15/1075
摘要： A method is provided for selecting membrane-translocating peptides (MTPs) from a peptide display library that are capable of crossing or penetrating a lipid membrane. A plurality of nucleic acid constructs that encode displayed peptides are expressed, resulting in the formation of a plurality of nucleic acid-peptide complexes, each complex comprising at least one displayed peptide associated with the corresponding nucleic acid construct encoding the displayed peptide; the complexes are exposed to a population of membrane-encapsulated compartments, allowing a translocating reaction to occur; complexes that remain unassociated with the membrane are removed; optionally complexes that are associated with the membrane are removed; and internalised nucleic acid-peptide complexes are recovered. The membrane-encapsulated compartments may be artificial vesicles such as liposomes, or populations of one or more cell types.
摘要翻译： 提供了从能够穿透或穿透脂质膜的肽展示文库中选择膜转位肽（MTP）的方法。 表达编码显示的肽的多个核酸构建体，导致形成多个核酸 - 肽复合物，每个复合物包含与编码所显示肽的相应核酸构建体相关联的至少一个显示的肽; 复合物暴露于膜包封的隔室群，允许发生易位反应; 与膜保持不相关的复合物被去除; 去除与膜相关的任选复合物; 并回收内化的核酸 - 肽复合物。 膜包封的隔室可以是人造囊泡，例如脂质体或一种或多种细胞类型的群体。
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公开(公告)号：US20140005126A1
公开(公告)日：2014-01-02
申请号：US13814536
申请日：2011-08-08
申请人： Chris Ullman , Agnes Jaulent , Seema Patel , Pascale Mathonet
发明人： Chris Ullman , Agnes Jaulent , Seema Patel , Pascale Mathonet
IPC分类号： C07K14/47
CPC分类号： C07K14/47 , C12N15/1044
摘要： A naive WW domain peptide library derived from a WW domain peptide sequence which has been diversified by changing the amino acid sequence at one or more positions is provided. The naive WW domain peptide library may be derived from a GroupIV WW domain peptide. Methods for making the naive WW domain peptide library and methods for selected a modified WW domain peptide that binds a target ligand using the naive WW domain peptide library are also provided. Also disclosed are modified WW domain peptides that bind desired target ligands, pharmaceutical compositions comprising such peptides, and uses for such peptides. The modified WW domain peptides have altered, improved or different, target ligand binding characteristics to those of the unmodified WW domain peptides from which they are derived.
摘要翻译： 提供了源自通过改变一个或多个位置上的氨基酸序列而多样化的WW结构域肽序列的初始WW结构域肽文库。 天真的WW结构域肽文库可以衍生自组IVWN结构域肽。 还提供了使用初始WW结构域肽文库制备初始WW结构域肽文库的方法和选择使用初始WW结构域肽文库结合靶配体的修饰的WW结构域肽的方法。 还公开了结合所需靶配体的修饰的WW结构域肽，包含这些肽的药物组合物，以及这些肽的用途。 修饰的WW结构域肽具有改变的，改进的或不同的靶配体结合特征，与未衍生的来自其的未修饰的WW结构域肽的配体结合特征。
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公开(公告)号：US08557744B2
公开(公告)日：2013-10-15
申请号：US11996496
申请日：2006-07-24
CPC分类号： C12N15/1075
摘要： A method is selects membrane-translocating peptides (MTPs) from a peptide display library that are capable of crossing or penetrating a lipid membrane. A plurality of nucleic acid constructs that encode displayed peptides are expressed, resulting in the formation of a plurality of nucleic acid-peptide complexes, each complex comprising at least one displayed peptide associated with the corresponding nucleic acid construct encoding the displayed peptide; the complexes are exposed to a population of membrane-encapsulated compartments, allowing a translocating reaction to occur; complexes that remain unassociated with the membrane are removed; optionally complexes that are associated with the membrane are removed; and internalized nucleic acid-peptide complexes are recovered. The membrane-encapsulated compartments may be artificial vesicles such as liposomes, or populations of one or more cell types.
摘要翻译： 一种方法是从能够穿透或穿透脂质膜的肽展示文库中选择膜 - 位移肽（MTP）。 表达编码显示的肽的多个核酸构建体，导致形成多个核酸 - 肽复合物，每个复合物包含与编码所显示肽的相应核酸构建体相关联的至少一个显示的肽; 复合物暴露于膜包封的隔室群，允许发生易位反应; 与膜保持不相关的复合物被去除; 去除与膜相关的任选复合物; 并回收内化的核酸 - 肽复合物。 膜包封的隔室可以是人造囊泡，例如脂质体或一种或多种细胞类型的群体。
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公开(公告)号：US20150057162A1
公开(公告)日：2015-02-26
申请号：US14385190
申请日：2013-03-15
申请人： Isogenica LTD.
IPC分类号： G01N33/68
CPC分类号： G01N33/6845 , C12N15/1034 , C12N15/1062 , C12N15/1075 , G01N2570/00
摘要： A method is disclosed for identifying a member of a peptide library that interacts with a target molecule in situ, the method including expressing immobilised nucleic acid molecules to produce the peptide library in a way that each member of the peptide library is immobilised on the nucleic acid molecule from which it was expressed; contacting the immobilised peptide library with the target molecule; and detecting an interaction between at least one member of the peptide library and the target molecule. The method further comprises sequencing the plurality of nucleic acid molecules in situ on the solid support, such that the at least one member of the peptide library that interacts with the target molecule can be immediately identified, at least by the sequence of the nucleic acid molecule from which it was expressed, without requiring additional or secondary analysis or characterising procedures in order to identify the useful members of the library. The target molecules may themselves be comprised within a second nucleic acid or peptide library.
摘要翻译： 公开了一种用于鉴定原位与靶分子相互作用的肽文库成员的方法，所述方法包括以固定在核酸上的肽文库的每个成员的方式表达固定的核酸分子以产生肽文库 分子表达; 使固定的肽文库与靶分子接触; 并检测肽文库的至少一个成员与靶分子之间的相互作用。 该方法还包括在固体支持物上原位测序多个核酸分子，使得可以至少通过核酸分子的序列立即鉴定与靶分子相互作用的肽文库中的至少一个成员 它被表达出来，而不需要额外的或次要的分析或特征化程序来识别图书馆的有用成员。 靶分子本身可以包含在第二核酸或肽文库中。
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公开(公告)号：US20130109616A1
公开(公告)日：2013-05-02
申请号：US13521457
申请日：2011-01-11
申请人： William Eldridge , Christopher Ullman , Marc Alan Fox , David Okhono Ulaeto , Joanne Elizabeth Thwaite
发明人： William Eldridge , Christopher Ullman , Marc Alan Fox , David Okhono Ulaeto , Joanne Elizabeth Thwaite
IPC分类号： C07K14/435
CPC分类号： C07K14/435 , C12N15/1075
摘要： A method is provided for isolating protease resistant antimicrobial peptides (AMPs) from a peptide display library. A plurality of nucleic acid constructs that encode displayed peptides are expressed, resulting in the formation of a plurality of peptide-nucleic acid complexes, each complex comprising at least one displayed peptide associated with the corresponding nucleic acid construct encoding the displayed peptide. The complexes are exposed to at least one protease, to allow the proteolysis of protease-sensitive peptides, such that resistant peptides remain. The peptide-nucleic acid complexes are further exposed to a membrane composition to allow association of complexes that contain membrane-associating peptides. Complexes that remain unassociated with the membrane are removed; and membrane-associated complexes are recovered. The AMPs so characterised may be resistant to one or more protease enzymes and exhibit antimicrobial activity against one or more microbe.
摘要翻译： 提供了用于从肽显示库分离抗蛋白酶抗性肽（AMP）的方法。 表达编码显示的肽的多个核酸构建体，导致形成多个肽 - 核酸复合物，每个复合物包含与编码所显示的肽的相应核酸构建体相关联的至少一个显示的肽。 将复合物暴露于至少一种蛋白酶，以允许蛋白酶敏感肽的蛋白水解，使得保留抗性肽。 肽 - 核酸复合物进一步暴露于膜组合物以允许包含膜缔合肽的复合物缔合。 与膜保持不相关的复合物被去除; 并回收膜相关复合物。 如此表征的AMP可能对一种或多种蛋白酶具有抗性并且对一种或多种微生物表现出抗微生物活性。
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公开(公告)号：US20110189164A1
公开(公告)日：2011-08-04
申请号：US11908790
申请日：2006-03-16
CPC分类号： C07K7/08 , C12N15/1034 , C12N15/1075
摘要： Peptide stabilizer compounds are provided that in combination with a biologically active peptide, can increase the protease elimination half-time of the biologically active peptide in vivo. The peptide stabilizer compounds are preferably in the form of peptide sequences that confer resistance to proteolysis upon conjugated biologically active peptides. Also provided is a method for the selection of novel proteolysis resistant compounds from in vitro generated libraries, and pharmaceutical compositions comprising the stabilizer compounds identified thereby.
摘要翻译： 提供了肽稳定剂化合物，其与生物活性肽的组合可以增加体内生物活性肽的蛋白酶消除半衰期。 肽稳定剂化合物优选为缀合的生物活性肽赋予蛋白水解抗性的肽序列形式。 还提供了用于从体外产生的文库中选择新的蛋白水解抗性化合物的方法，以及包含由其鉴定的稳定剂化合物的药物组合物。
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