Periodic Reporting for period 1 - TARGET (Targeting the "untargetable" by merging biological and chemical compound libraries)
Período documentado: 2022-01-01 hasta 2023-06-30
The project TARGET aims at developing and applying a novel method for targeting so-called "undruggable" proteins by tapping into a new chemical space, generated by "merging" biological and chemical compound libraries. The new methods should deliver synthetic ligands to notoriously difficult-to-target proteins as for example challening intracellular protein-protein interactions. Such ligands would offer ideal starting points for developing new therapeutics to address important unmet medical needs.
The core idea of the TARGET project is to merge biological and chemical compound libraries, the first library type being generated by ribosomal translation (e.g. phage display peptide libraries) and the second one by chemical synthesis. The two types of libraries have their strengths and weaknesses and were so far used mostly independently from each other in drug development. With biological libraries, it is possible to generate and screen more than a billion random peptides but the chemical diversity of these libraries is small (e.g. in phage display libraries, the building blocks are mostly limited to the 20 natural amino acids). In contrast, chemical libraries are structurally highly diverse and can be generated using a nearly endless number of building blocks, but the number of molecules that can be handled and screened is limited. In the TARGET project, biological compound libraries (phage-displayed peptides) are chemically diversified with large numbers of chemical building blocks of structurally and chemically highly diverse fragments, to generate and screen a previously unseen large and structurally highly diverse chemical space.
If successful, the project will deliver cell permeable ligands for currently intractable targets and offer the basis for developing new drugs and addressing major diseases.
The core idea of the TARGET project is to merge biological and chemical compound libraries, the first library type being generated by ribosomal translation (e.g. phage display peptide libraries) and the second one by chemical synthesis. The two types of libraries have their strengths and weaknesses and were so far used mostly independently from each other in drug development. With biological libraries, it is possible to generate and screen more than a billion random peptides but the chemical diversity of these libraries is small (e.g. in phage display libraries, the building blocks are mostly limited to the 20 natural amino acids). In contrast, chemical libraries are structurally highly diverse and can be generated using a nearly endless number of building blocks, but the number of molecules that can be handled and screened is limited. In the TARGET project, biological compound libraries (phage-displayed peptides) are chemically diversified with large numbers of chemical building blocks of structurally and chemically highly diverse fragments, to generate and screen a previously unseen large and structurally highly diverse chemical space.
If successful, the project will deliver cell permeable ligands for currently intractable targets and offer the basis for developing new drugs and addressing major diseases.