Ligational encoding of small molecules

A method for synthesising one or more bifunctional complexes each comprising a molecule resulting from the reaction of a plurality of chemical entities and an identifier polynucleotide identifying one or more of the chemical entities having participated in the synthesis of the molecule, said method comprising the steps of

• i. providing a plurality of building blocks each comprising an oligonucleotide associated with one or more chemical entities,
• ii. providing at least one connector oligonucleotide capable of hybridising with one or more building block oligonucleotides,
• iii. immobilising at least one building block to a solid support,
• iv. hybridising said immobilized building block oligonucleotide to a first connector oligonucleotide,
• v. hybridising at least one additional building block oligonucleotide to said first connector oligonucleotide,
• vi. covalently ligating each building block oligonucleotide to at least one other building block oligonucleotide, at least one of said covalently ligated building block oligonucleotides being hybridised to the connector oligonucleotide,
• vii. separating the connector polynucleotide from the ligated building block oligonucleotides,
• viii. reacting one or more chemical entities associated with different building block oligonucleotides, thereby obtaining a first bifunctional complex comprising a first molecule or first molecule precursor linked to a first identifier oligonucleotide identifying the chemical entities having participated in the synthesis of the molecule or molecule precursor, wherein said first bifunctional complex is immobilised to a solid support.

A method for synthesising a bifunctional complex comprising a molecule resulting from the reaction of a plurality of chemical entities, wherein said molecule is linked to an identifier polynucleotide identifying one or more of the chemical entities having participated in the synthesis of the molecule, said method comprising the steps of

• i) providing a plurality of building blocks selected from the group consisting of
• a) building blocks comprising an identifier oligonucleotide linked to one or more chemical entities,
• b) building blocks comprising an identifier oligonucleotide linked to one or more reactive groups, and
• c) building blocks comprising an identifier oligonucleotide comprising a spacer region, wherein said building blocks comprising a spacer region are preferably connector polynucleotides to which building blocks of groups a) and b) can hybridise,
• ii) generating a hybridisation complex comprising at least n building blocks by hybridising the identifier oligonucleotide of one building block to the identifier oligonucleotide of at least one other building block,
• wherein n is an integer of 4 or more
• wherein at least 3 of said at least n building blocks comprise a chemical entity,
• wherein no single identifier oligonucleotide is hybridised to all of the remaining identifier oligonucleotides,
• wherein optionally at least one of said building blocks of group c) is immobilised to a solid support, thereby providing a handle to which an oligonucleotide of at least one building block of groups a) or b) can hybridise,
• iii) covalently linking identifier oligonucleotides of building blocks comprising one or more chemical entities, thereby obtaining an identifier polynucleotide comprising covalently linked identifier oligonucleotides each associated with one or more chemical entities,
• iv) optionally separating said identifier polynucleotide obtained in step iv) from any immobilised connector oligonucleotides hybridized thereto, wherein said separation optionally comprises the step of diverting said identifier polynucleotide comprising covalently linked identifier oligonucleotides each associated with one or more chemical entities to a different reaction compartment, thereby separating said identifier polynucleotide from said immobilised connector oligonucleotides
• v) reacting said at least 3 chemical entities linked to the identifier polynucleotide, and
• vi) obtaining a bifunctional complex comprising a molecule resulting from the reaction of a plurality of chemical entities, wherein said molecule is linked to an identifier polynucleotide identifying one or more of the chemical entities having participated in the synthesis of the molecule.