Abstract
The scope of targets investigated in pharmaceutical research is continuously moving into uncharted territory. Consequently, finding suitable chemical matter with current compound collections is proving increasingly difficult. Encoded library technologies enable the rapid exploration of large chemical space for the identification of ligands for such targets. These binders facilitate drug discovery projects both as tools for target validation, structural elucidation and assay development as well as starting points for medicinal chemistry. Novartis internalized two complementing encoded library platforms to accelerate the initiation of its drug discovery programs. For the identification of low-molecular weight ligands, we apply DNA-encoded libraries. In addition, encoded peptide libraries are employed to identify cyclic peptides. This review discusses how we apply these two platforms in our research and why we consider it beneficial to run both pipelines in-house.
Highlights
Advances in disease characterization and target identification [1,2] constantly move the drug discovery portfolio into unchartered territory
More and more emerging targets are attractive from a pathological point, but are at the same time challenging to modulate with established low molecular weight (LMW) compounds or biologic agents
Ring closure reduces conformational freedom and results in peptides with higher affinity and selectivity compared to their linear counterparts [31]. These limitations markedly decrease the accessible chemical space and a method combining the advantage of the diversity of LMW libraries and sequence multitude of genetically encoded approaches is desirable
Summary
Advances in disease characterization and target identification [1,2] constantly move the drug discovery portfolio into unchartered territory. One way to cope with that is to considerably enlarge the chemical space available to current hit finding methods (Figure 1) This is underlined by the fact that the size of compound libraries is normally limited to a range of about 106 mostly due to archive and screening logistics. DNA-encoded libraries (DEL) resemble LMW molecules, but offer the opportunity to screen up to 109 and more possible chemical entities This size is 1’000-fold larger than a usual compound collection of pharmaceutical companies and significantly increases the chances of finding new chemical starting points. Peptides with a typical length of 5–20 amino acids have an intermediate size and are able to interact with target proteins in many ways, covering large largesurfaces surfacesoror small binding pockets.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
