Patent ID: 9574189
Date: 2017-02-21
CPC Classifications: C12N,C40B

Claim:
1. A method for the synthesis of a bifunctional complex comprising a molecule and a single stranded oligonucleotide identifier attached to the molecule, said method comprising the steps of i) providing a display oligonucleotide attached to ii) providing a first reactant comprising one or more chemical entities and one or more reactive groups capable of reacting with iii) providing a first oligonucleotide tag capable of hybridising to part of a first oligonucleotide anti-tag, wherein the first oligonucleotide tag identifies the first reactant and, optionally, the further first reactant, iv) providing a first oligonucleotide anti-tag capable of hybridising to at least part of the first oligonucleotide tag provided in step iii) and to at least part of the display oligonucleotide provided in step i), v) reacting the first reactant provided in step ii) with c) the one or more chemical reaction site(s) of the display oligonucleotide and/or with d) the one or more reactive groups of the first further reactant comprising one or more chemical entities, vi) hybridising the first anti-tag to the display oligonucleotide and to the first oligonucleotide tag, vii) enzymatically ligating the display oligonucleotide and the first oligonucleotide tag to form a nascent bifunctional complex, viii) providing a second reactant comprising one or more chemical entities and one or more reactive groups capable of reacting with ix) providing a second oligonucleotide tag capable of hybridising to part of a second oligonucleotide anti-tag, wherein the second oligonucleotide tag identifies the second reactant and, optionally, the further second reactant, x) providing a second oligonucleotide anti-tag capable of hybridising to part of the first oligonucleotide tag provided in step iii) and to part of the second oligonucleotide tag provided in step ix), xi) reacting the second reactant provided in step viii) with c) the chemical reaction site(s) of the display oligonucleotide and/or d) one or more reactive groups of one or more reactant(s) having reacted in a previous synthesis round and/or e) one or more reactive groups of a further second reactant comprising one or more chemical entities, xii) hybridising the second anti-tag to the first oligonucleotide tag and the second oligonucleotide tag, xiii) enzymatically ligating the first and second oligonucleotide tags in the absence of ligation the first and second anti-tag oligonucleotides to provide a bifunctional complex comprising an oligonucleotide identifier having ligated first and second oligonucleotide tags hybridized with unligated first and second anti-tag oligonucleotides xiv) displacing the unligated anti-tags from the bifunctional complex of step (xii) to provide a bifunctional complex comprising a molecule and a single stranded oligonucleotide identifier comprising tags identifying the reactants which participated in the synthesis of the molecule, xv) hybridising a primer to the 3′-end of the single stranded oligonucleotide identifier comprising tags identifying the reactants which participated in the synthesis of the molecule, and xvi) extending the primer by a polymerase extension reaction to generate a double stranded identifier oligonucleotide.