Dual-pharmacophore DNA-encoded chemical libraries

• DNA-encoded chemical libraries represent promising tools for ligand discovery.
• DNA-encoded chemical libraries can be practiced in single-pharmacophore and dual-pharmacophore format.
• Novel technologies allow the decoding of dual-pharmacophore libraries by DNA sequencing.
• Dual-pharmacophore chemical libraries are useful for de novo discovery and for affinity maturation.

In contrast to single-pharmacophore DNA-encoded libraries, where only one chemical moiety is linked to DNA, dual-pharmacophore DNA-encoded chemical libraries feature the display of two independent small-molecules in close proximity. This, in principle, allows to explore adjacent epitopes on a pharmaceutical target of choice and hence the discovery of simultaneously binding pairs of fragments, by virtue of the chelate effect.