Methods for tagging dna-encoded libraries

摘要

A method of tagging a first library comprising an oligonucleotide-encoded small molecule or peptide is disclosed. A headpiece having a first functional group and a second functional group is provided in step (i). The headpiece comprises at least one 2’-substituted nucleotide and the headpiece comprises a 2’-substituted nucleotide at the 5’-terminus and/or 3’-terminus. In step (ii) the first functional group of the headpiece is bound to a first component of the small molecule or peptide. The headpiece is directly connected to the first component or the headpiece is indirectly connected to the first component by a bifunctional linker; and in step (iii) the second functional group of the headpiece is bound to a first building block tag to form a complex. The steps (ii) and (iii) can be performed in any order and the first building block tag encodes for the binding reaction of the step (ii), thereby providing a tagged library. A complex comprises a headpiece and a building block tag. The tag comprises from 5 to 20 nucleotides, a 2’-substituted nucleotide at the 5’-terminus, and a 2’- substituted nucleotide at the 3’-terminus and the headpiece is directly connected to a small molecule or peptide or the headpiece is indirectly connected to a small molecule or peptide by a bifunctional linker.