Groupe du prof. Lubell
Titre: Synthesis of Cyclic β- and γ- Amino Acids and Ribosomal Elongation using a Reprogrammed Genetic Code
Cyclic building blocks offer much-needed potential to improve potency and bioavailability in the search for complex biologically active molecules. Among them, the peptide market is valued at $28.5 billion with an expected growth rate of 10% per year between 2021 and 2026. However, peptides suffer from limitations such as stability in the human body. The search for new building blocks is necessary and of great impact as they can improve bioavailability and pharmacokinetic properties to enhance in vivo stability. The synthesis of amino acid building blocks is being pursued using a novel Zn/Cu catalyzed SN2' selective carbon-carbon bond formation reaction as a key step. The enantiomerically pure β- and γ- cyclic amino acids will be integrated into the Random nonstandard Peptide Integrated Discovery (RaPID) synthesis and screening platform which offers potential to employ unnatural amino acids to prepare up to 10^12 macrocyclic peptides using in vitro ribosomal synthesis and RNA display.
