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    • 3. 发明申请
    • PROXIMITY-AIDED SYNTHESIS OF TEMPLATED MOLECULES
    • 近模助分解模板分子的合成
    • WO2004024929A3
    • 2004-05-06
    • PCT/DK0300590
    • 2003-09-12
    • NUEVOLUTION ASFRANCH THOMASTHISTED THOMAS
    • FRANCH THOMASTHISTED THOMAS
    • C12N15/10C07B61/00C12P19/34C12Q1/68
    • 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.
    • 公开了用于合成双功能复合物的方法。 该复合物包含模板以及分子,其合成由模板引导。 he复合物的合成首先需要a)包含两个或更多个序列密码子的模板,第一对分子亲和对和反应基团; 和b)两个或更多个构件,每个构件包含i)能够识别模板密码子的反密码子,ii)包含至少一个反应基团的功能实体,以及iii)连接反密码子 以及功能实体,其中具有意欲与反应性基团远端的模板的密码子相互作用的反密码子的构建块包含分子亲和对的第二部分作为接头的一部分。 通过c)进行合成,c)使模板与构建模块在允许结构单元的反密码子与模板的密码子特异性杂交的条件下和在确保分子对的部分(如果存在的话)的组装 ; 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,获得构件的功能实体与模板之间的连接,e)裂解键以获得新生模板化分子,f)分离 分子亲和对,和g)对于具有能够与新密码子杂交的反密码子的结构单元,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利用分子进化技术就优选复合物而言富集的文库。