Structure-diverse Phylomer libraries as a rich source of bioactive hits from phenotypic and target directed screens against intracellular proteins.

Phylomers are peptides derived from biodiverse protein fragments. Genetically encoded Phylomer libraries have been constructed, containing hundreds of billions of peptides derived from virtually all of the few thousand fold families found in the protein universe. They offer a rich source of high quality hits against diverse target sequences and have been used for three main purposes: firstly, to identify and validate targets in phenotypic screens; secondly, to block protein interactions with nanomolar potency binding affinities; thirdly as a source of more efficient cell penetrating peptides for the delivery of a wide range of biologics. Phylomer libraries are being increasingly used in applications such as phenotypic screening where the numbers of peptides which can be feasibly screened is limited. Phylomers also offer access to the intracellular target landscape, which remains largely undruggable by conventional means.