L09 - Chemical Approaches for Next Generation Peptide Therapeutics

In the last years, the development of new synthetic strategies in the peptide chemistry field has significantly accelerated the peptide development process contributing to the increased number of approved drugs on the market. Innovative drugs are being developed based on peptides and small proteins as key players in physiological pathways, including actions as hormones, neurotransmitters, growth factors, ion channel ligands. Moreover macrocycles are now establishing as a new modality for targeting protein/protein interactions, with the great acceleration driven by phage and mRNA display technologies, where large libraries are screened for the identification of novel and potent macrocyclic peptide leads. In the discovery process, a peptide lead is optimized to acquire drug-like status by fine tuning its properties such as activity towards the target, selectivity, chemical and metabolic- stability and desired half-life profile. To accomplish these goals, a full repertoire of advanced synthetic strategies is needed. State-of-the-art synthesis in solution, high performance solid phase synthesis, native chemical ligation and the access to a  larger diversity in the chemical space through non-natural amino acids are essential to support the development of candidates having  the requested profile.  A journey through novel and advanced synthetic strategies applied to target molecules in a wide molecular weight range will show how chemical tools are key players in the successful development of new peptide drugs.