The isolation of specific binding molecules is a central problem in the drug discovery process. Through its daughter company Philochem, Philogen has generated a series of DNA-encoded chemical libraries which represent a new tool for the efficient identification of ligands to target proteins of choice.
Such libraries consist of a collection of organic molecules each covalently coupled to a distinctive DNA tag that serves as amplifiable identification bar code.
The implementation of next generation high-throughput sequencing now allows the identification of binding molecules from DNA-encoded libraries of unprecedented size. DNA-encoded chemical libraries can be used for the affinity capture of binders to virtually any given target protein, without the need for a screening assay, which allows tackling of historically difficult target proteins such as components of protein-protein interactions.

Schematic representation ofan organic molecule isolated fron Philogen’s DNA-Encoded Chemical Libraries binding the target of choice.

Most drug development programs start with the isolation of a binding molecule to a pharmacologically relevant target protein. Technologies for the isolation of such binding molecules are therefore of central importance for drug discovery.
While antibodies against virtually any given target can nowadays be raised in just few days using biological display methodologies (i.e., antibody phage-display) there is a great need for rapid and efficient techniques towards the isolation of small organic binders.
In high-throughput screening campaigns, large collections of chemical compounds are individually screened in parallel in miniaturized in vitro assays for binding to the target protein of interest. These assays typically require the availability of an enzymatic assay or a ligand for a displacement assay. Such discovery campaigns are sometimes unsuccessful, thus preventing drug development even though suitable target protein for pharmacological intervention may be available. DNA-encoded chemical libraries promise to revolutionize the way organic ligands to pharmaceutical targets are isolated.

Schematic representation of display methodologies for the construction of large repertoires of macromolecules or smaller organic molecules.
Left: Antibody fragments in scFv format are displayed on the surface of filamentous phage as a fusion to the minor coat protein pIII, thus yielding a link between protein binding properties ('phenotype') and genetic information coding for the antibody ('genotype').
Right: The conceptual translation of antibody phage display technology has led to the development of DNA-encoded chemical libraries, in which individual organic molecules are covalently linked to a unique and PCR-amplifiable DNA tag.