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    • 1. 发明申请
    • LIGATIONAL ENCODING OF SMALL MOLECULES
    • 小分子的编码
    • WO2004083427A3
    • 2005-02-17
    • PCT/DK2004000195
    • 2004-03-22
    • NUEVOLUTION ASFRANCH THOMASJACOBSEN SOEREN NYBOERASMUSSEN TORBENNEVE SOERENPEDERSEN HENRIKGOULIAEV ALEX HAAHR
    • FRANCH THOMASJACOBSEN SOEREN NYBOERASMUSSEN TORBENNEVE SOERENPEDERSEN HENRIKGOULIAEV ALEX HAAHR
    • C12N15/10C12P21/02
    • C07H21/04C12N15/1068C12P21/02C40B40/06C40B50/04
    • 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.
    • 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联的抗密码子,和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。
    • 2. 发明申请
    • LIGATIONAL ENCODING OF SMALL MOLECULES
    • 小分子的编码
    • WO2004083427A2
    • 2004-09-30
    • PCT/DK2004/000195
    • 2004-03-22
    • NUEVOLUTION A/SFRANCH, ThomasJACOBSEN, Soeren, NyboeRASMUSSEN, TorbenNEVE, SoerenPEDERSEN, HenrikGOULIAEV, Alex, Haahr
    • FRANCH, ThomasJACOBSEN, Soeren, NyboeRASMUSSEN, TorbenNEVE, SoerenPEDERSEN, HenrikGOULIAEV, Alex, Haahr
    • C12N15/10
    • C07H21/04C12N15/1068C12P21/02C40B40/06C40B50/04
    • 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.
    • 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联的抗密码子,和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。
    • 9. 发明申请
    • ENCODED MOLECULES BY TRANSLATION (EMT)
    • 编码分子通过翻译(EMT)
    • WO2004110964A3
    • 2005-03-31
    • PCT/DK2004000416
    • 2004-06-15
    • NUEVOLUTION ASPEDERSEN HENRIKFRANCH THOMAS
    • PEDERSEN HENRIKFRANCH THOMAS
    • C07B61/00C12N15/10C12N15/67
    • C12N15/1062C12N15/1068C12N15/67
    • The present invention is directed to methods for the synthesis, selection, amplification and isolation of templated molecules having desirable properties. The invention makes it possible to synthesise a variety of different templated molecules other than alpha-peptides and modified alpha-peptides. In particular, the present invention enables synthesis of templated molecules such as beta -, ϒ -, ϖ peptides, carbopeptoids, vinylogous peptides, oligoanthrilamides, oligoureas, azapeptides (azatides), oligocarbamates, PNA, oligopyrrolinones, vinylogous sulfonamidopeptide, peptoids, azapeptoids and hydrazino peptides. It is possible in accordance with the methods of the invention to synthesise templated molecules comprising heterocyclic components, such as coumarins and quinolones, pyrazolone, isoxazolone, pyrimidiones, phtalhydrazides, diketopiperazines, hydantoins, and benzodiazepines.
    • 本发明涉及用于合成,选择,扩增和分离具有所需性质的模板分子的方法。 本发明使得可以合成除α-肽和修饰的α-肽以外的各种不同的模板分子。 特别地,本发明能够合成模板分子,例如β - ,Υ-,π肽,卡皮派,血液肽,寡聚甲酰胺,寡聚脲,azapeptides(azatides),oligocarbamates,PNA,oligopyrrolinones,vinylogous sulfamidopeptide,peptoids,azapeptoids和hydrazino 肽。 可以根据本发明的方法合成包含杂环成分的模板分子,例如香豆素和喹诺酮类,吡唑啉酮,异恶唑酮,嘧啶,邻苯二甲酰肼,二酮哌嗪,乙内酰脲和苯并二氮杂。
    • 10. 发明申请
    • PROXIMITY-AIDED SYNTHESIS OF TEMPLATED MOLECULES
    • 临床合成的模板分子
    • WO2004024929A2
    • 2004-03-25
    • PCT/DK2003/000590
    • 2003-09-12
    • NUEVOLUTION A/SFRANCH, ThomasTHISTED, Thomas
    • FRANCH, ThomasTHISTED, Thomas
    • C12P
    • C12N15/1068
    • Disclosed is a method for synthesising a bifunctional complex. The complex comprises a template as well as a molecule, the synthesis of which being directed by the template. The synthesis of he complex requires initially a) a template comprising two or more codons in sequence, a first pair of a molecular affinity pair, and a reactive group; and b) two or more building blocks, each building block comprises i) an anti-codon capable of recognising a codon of the template, ii) a functional entity comprising at least one reactive group, and iii) a linker connecting the anti-codon and the functional entity, wherein building blocks having anti-codons intended to interact with codons of the template distal to the reactive group comprise as a section of the linker a second part of the molecular affinity pair. The synthesis proceeds by c) contacting the template with a building block under conditions which allow specific hybridisation of the anti-codon of the building block to the codon of the template, and under conditions ensuring assembling of the parts of the molecule pair, if present; d) obtaining a connection between the functional entity of the building block and the template by a reaction involving the template reactive group and the functional entity reactive group, e) cleaving a linkage to obtaining a nascent templated molecule, f) separating the parts of the molecular affinity pair, and g) repeating, for a building block having an anti-codon capable of hybridising to a new codon, steps c) to f) one or more times. The complexes obtainable according the invention may be used in the generation of a library which may be enriched with regard to preferred complexes using molecular evolution techniques.
    • 公开了合成双功能复合物的方法。 复合物包括模板以及分子,其合成由模板引导。 他复合物的合成最初需要a)包含序列中两个或多个密码子的模板,第一对分子亲和力对和反应性基团; 和b)两个或更多个构建块,每个构建块包括i)能够识别模板密码子的抗密码子,ii)包含至少一个反应性基团的功能实体,和iii)连接反密码子 和功能性实体,其中具有旨在与远离反应性基团的模板的密码子相互作用的抗密码子的构建体包含分子亲和力对的第二部分作为连接体的一部分。 合成是通过以下步骤进行的:c)在允许构建块的抗密码子与模板的密码子特异性杂交的条件下,以及在确保组装分子对的部分(如果存在)的条件下,将模板与构建块接触 ; d)通过涉及模板反应性基团和功能性实体反应性基团的反应获得构建单元的功能性实体与模板之间的连接,e)切割连接以获得新生的模板分子,f)将 分子亲和力对,以及g)对于具有能够与新密码子杂交的抗密码子的构建嵌段,重复步骤c)至f)一次或多次。 根据本发明可获得的复合物可用于产生可以使用分子进化技术关于优选的复合物富集的文库。