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1. 发明申请

US20080305957A1 Method for Obtaining Structural Information Concerning an Encoded Molecule and Method for Selecting Compounds 审中-公开
标题翻译：获得编码分子结构信息的方法和选择化合物的方法
公开(公告)号：US20080305957A1
公开(公告)日：2008-12-11
申请号：US10572644
申请日：2004-09-17
申请人： Thomas Thisted , Mikkel Dybro Lundorf , Per-Ola Freskgard , Torben Ravn Rasmussen
发明人： Thomas Thisted , Mikkel Dybro Lundorf , Per-Ola Freskgard , Torben Ravn Rasmussen
IPC分类号： C40B20/04
CPC分类号： C12Q1/6837 , C12N15/1068 , C12Q1/6811 , C12Q2531/113 , C12Q2565/501
摘要： In one aspect, the present invention relates to a method for obtaining structural information about an encoded molecule. The encoded molecule may be produced by a reaction of a plurality of chemical entities and may be capable of being connected to an identifier oligonucleotide containing codons informative of the identity of the chemical entities which have participated in the formation of the encoded molecule. In a certain embodiment, primers are designed complementary to the codons appearing on the identifier oligonucleotide, and the presence, absence or relative abundance of a codon is evaluated by mixing a primer with the identifier oligonucleotide in the presence of a polymerase and substrate (deoxy)ribonucleotide triphosphates and measuring the extension reaction. In another aspect, the invention provides a method for selecting compounds which binds to a target. More specifically, the invention relates to a method in which a target associated with an oligonucleotide initially is mixed with a library of complexes, each complex comprising a display molecule and an oligonucleotide identifying said display molecule. Next, due an increased proximity, the target oligonucleotide is coupled to the identifier oligonucleotide of complexes having a display molecule with affinity towards the target. In a final stage the coupled nucleotides are analysed to deduce at least the identity of the display molecule.
摘要翻译：一方面，本发明涉及获得关于编码分子的结构信息的方法。编码的分子可以通过多个化学实体的反应产生，并且可以能够连接到含有密码子的标识符寡核苷酸，该密码子包括参与编码分子形成的化学实体的身份。在一些实施方案中，设计引物与出现在标识寡核苷酸上的密码子互补，并且通过在聚合酶和底物（脱氧））存在下将引物与标识寡核苷酸混合来评估密码子的存在，不存在或相对丰度，核糖核苷三磷酸并测量延伸反应。另一方面，本发明提供了选择与靶标结合的化合物的方法。更具体地，本发明涉及一种方法，其中与寡核苷酸相关的靶标最初与复合物文库混合，每个复合物包含显示分子和识别所述显示分子的寡核苷酸。接下来，由于接近度增加，靶寡核苷酸与具有与靶具有亲和性的显示分子的复合物的标识符寡核苷酸偶联。在最后阶段，分析耦合的核苷酸以至少推断显示分子的身份。

2. 发明授权

US07915201B2 Ligational encoding of small molecules 有权
标题翻译：小分子的编码编码
公开(公告)号：US07915201B2
公开(公告)日：2011-03-29
申请号：US10549619
申请日：2004-03-22
申请人： Thomas Franch , Soeren Nyboe Jacobsen , Torben Ravn Rasmussen , Soeren Neve , Henrik Pedersen , Alex Haahr Gouliaev
发明人： Thomas Franch , Soeren Nyboe Jacobsen , Torben Ravn Rasmussen , Soeren Neve , Henrik Pedersen , Alex Haahr Gouliaev
IPC分类号： C40B50/00 , C40B30/00
CPC分类号： C07H21/04 , C12N15/1068 , C12P21/02 , C40B40/06 , C40B50/04
摘要： The invention relates to a method for synthesising a bifunctional complex comprising an encoded molecule and an identifier polynucleotide identifying the chemical entities having participated in the synthesis of the encoded molecule, said method comprising the steps of i) providing a) at least one template comprising one or more codons capable of hybridising to an anti-codon, wherein said template is optionally associated with one or more chemical entities, and b) a plurality of building blocks each comprising an anti-codon associated with one or more chemical entities, and ii) hybridising the anti-codon of one or more of the provided building blocks to the template, iii) covalently linking said anti-codons and/or linking the at least one template with the anti-codon of at least one building block, thereby generating an identifier polynucleotide capable of identifying chemical entities having participated in the synthesis of the encoded molecule, iv) separating the template from one or more of the anti-codons hybridised thereto, thereby generating an at least partly single stranded identifier polynucleotide associated with a plurality of chemical entities, v) generating a bifunctional complex comprising an encoded molecule and an identifier polynucleotide identifying the chemical entities having participated in the synthesis of the encoded molecule, wherein said encoded molecule is generated by reacting at least two of said plurality of chemical entities associated with the identifier polynucleotide, and wherein said at least two chemical entities are provided by separate building blocks.
摘要翻译：本发明涉及一种合成双功能复合物的方法，所述双功能复合物包含编码分子和识别已经参与编码分子合成的化学实体的标识多核苷酸，所述方法包括以下步骤：i）提供a）至少一个包含一个或更多能够与抗密码子杂交的密码子，其中所述模板任选地与一个或多个化学实体相关联，以及b）多个结构单元，每个结构单元包含与一个或多个化学实体相关的抗密码子，以及ii）将一个或多个所提供的构建块的抗密码子与模板杂交，iii）共价连接所述抗密码子和/或将至少一个模板与至少一个构建块的抗密码子连接，由此产生能够识别已经参与编码分子的合成的化学实体的标识符多核苷酸，iv）将模板从一个或多个分离出来更多的与其杂交的抗密码子，从而产生与多个化学实体相关联的至少部分单链标识多核苷酸，v）产生包含编码分子的双功能复合物和识别参与合成的化学实体的标识符多核苷酸的编码分子，其中所述编码的分子通过使与所述标识多核苷酸相关联的所述多个化学实体中的至少两个反应而产生，并且其中所述至少两个化学实体由单独的构建块提供。

3. 发明授权

US11118215B2 Method for obtaining structural information concerning an encoded molecule and method for selecting compounds 有权
公开(公告)号：US11118215B2
公开(公告)日：2021-09-14
申请号：US10572644
申请日：2004-09-17
申请人： Thomas Thisted , Mikkel Dybro Lundorf , Per-Ola Freskgard , Torben Ravn Rasmussen
发明人： Thomas Thisted , Mikkel Dybro Lundorf , Per-Ola Freskgard , Torben Ravn Rasmussen
IPC分类号： C40B20/04 , C12Q1/6837 , C12N15/10 , C12Q1/6811
摘要： In one aspect, the present invention relates to a method for obtaining structural information about an encoded molecule. The encoded molecule may be produced by a reaction of a plurality of chemical entities and may be capable of being connected to an identifier oligonucleotide containing codons informative of the identity of the chemical entities which have participated in the formation of the encoded molecule. In a certain embodiment, primers are designed complementary to the codons appearing on the identifier oligonucleotide, and the presence, absence or relative abundance of a codon is evaluated by mixing a primer with the identifier oligonucleotide in the presence of a polymerase and substrate (deoxy)ribonucleotide triphosphates and measuring the extension reaction. In another aspect, the invention provides a method for selecting compounds which binds to a target. More specifically, the invention relates to a method in which a target associated with an oligonucleotide initially is mixed with a library of complexes, each complex comprising a display molecule and an oligonucleotide identifying said display molecule. Next, due an increased proximity, the target oligonucleotide is coupled to the identifier oligonucleotide of complexes having a display mole-cute with affinity towards the target. In a final stage the coupled nucleotides are analysed to deduce at least the identity of the display molecule.

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