Synthesis of peptide double rings with new multicomponent strategies.
IPB scientists and partners from Havana have developed two novel synthesis strategies for the successful assembly of bicyclic peptides that exhibit interconnected and fused ring topologies. Both multicomponent macrocyclization methods allow simultaneous ring closure or linkage of the resulting rings via a lactam bridge. The first approach involves the assembly of two linked β-turns in which a double Ugi reaction provides peptide linkage and dimerization. The second approach - a resin-bound Ugi macrocyclization - leads to the assembly of lactam-bridged macrocycles with stable tertiary folds. Both strategies are conceptually novel, especially in the way the multicyclic peptide architectures are assembled. This is because the multicomponent reactions are employed not only to close a macrocyclic ring and thus fix a secondary structure, but also to enable the formation of the complex macrobicyclic architecture. Accordingly, the methods are promising for the development of new peptide drugs, the scientists conclude.
Macrocyclic peptides can mimic specific protein structures or act as important components in peptide-drug conjugates. They are increasingly used to fix specific bioactive conformations and improve their pharmacological properties.
