Nucleic acid complexes for screening barcoded compounds

A method comprising

• contacting (1) a plurality of nucleic acid complexes each conjugated to a first binding partner and a second binding partner with (2) a plurality of candidate ligands each conjugated to a distinct/unique nucleic acid barcode,
• physically separating (1) nucleic acid complexes having the first binding partner bound to the second binding partner and to the candidate ligand from (2) other nucleic acid complexes, and
• identifying the candidate ligand bound to the first binding partner by nucleic acid sequencing of the nucleic acid barcode,
• wherein each nucleic acid complex comprises a single-stranded scaffold nucleic acid hybridized to a plurality of single-stranded oligonucleotides, wherein a first single-stranded oligonucleotide in the plurality is linked to the first binding partner and a second single-stranded oligonucleotide in the plurality is linked to the second binding partner,
• wherein the first binding partner and the second binding partner do not bind to each other unless the candidate ligand is bound to the first binding partner.

A method comprising

• contacting a target with a candidate ligand conjugated to a nucleic acid barcode, wherein the target and optionally the candidate ligand are bound to a nucleic acid complex that is further bound to an active-target-specific binding partner and an inactive-target-specific binding partner,
• isolating a target bound to a candidate ligand and an active-target-specific binding partner, and
• identifying the candidate ligand bound to the target by nucleic acid sequencing of the nucleic acid barcode,
• wherein the nucleic acid complex comprises a single-stranded scaffold nucleic acid hybridized to a plurality of single-stranded oligonucleotides, wherein a first single-stranded oligonucleotide is linked to the target and a second single-stranded oligonucleotide is linked to the active-target-specific binding partner,
• wherein the target does not bind to the active-target-specific binding partner in the absence of the candidate ligand.

A method comprising

• contacting (1) a nucleic acid complex conjugated to a first binding partner and a second binding partner with (2) a candidate ligand conjugated to a nucleic acid barcode, wherein the first binding partner has affinity for the second binding partner in the absence of the candidate ligand,
• isolating a nucleic acid complex having the first binding partner bound to the candidate ligand and not bound to the second binding partner, and
• identifying the candidate ligand bound to the first binding partner by nucleic acid sequencing of the nucleic acid barcode,
• wherein the nucleic acid complex comprises a single-stranded scaffold nucleic acid hybridized to a plurality of single-stranded oligonucleotides, wherein a first single-stranded oligonucleotide in the plurality is linked to the first binding partner and a second single-stranded oligonucleotide in the plurality is linked to the second binding partner,
• wherein the second binding partner and the candidate ligand are different from each other.