Peptides, and in particular macrocyclic peptides, are well known for their ability to disrupt protein-protein interactions (PPIs). However, it's challenging to screen for and discover novel macrocyclic peptides. High throughput screening compound collections generally include few such molecules, and other techniques are limited to macrocycles comprised of naturally occurring (or similar) amino acids.
In this presentation we will discuss the use of DNA encoded libraries to discover peptide macrocycles that disrupt PPIs and provide a case study employing the oncoprotein murine double minute 2 (MDM2). We will also highlight the advantages of DEL compared to other methods, which includes the ability to use unnatural amino acids. This provides greater chemical diversity with smaller ring sizes and facilitates subsequent hit development as it pertains to beneficial PK properties.
Key Learning Objectives:
- Learn the potential advantages of using DEL for discovering cell-permeable cyclic peptides
- Learn the basics of how such DELs are designed and the current status of the field
- Learn how to follow up on DEL hits and some discussion of emerging techniques
- Get a sense of timelines and difficulties that exist when conducting such a screen
Who Should Attend:
- Researchers interested in macrocyclic peptides, in particular cell permeable peptides
- Researchers struggling to find chemical matter capable of inhibiting PPIs