Lecture “Multicomponent Synthesis of Macrocyclic and Stapled Peptides”
On 4 October at 16:30 p.m. (Moscow time)
This lecture highlights the development of a methodology that provides a repertoire of synthetic tools for the achievement of N-alkylated, macrocyclic peptides, including inhibitors of protein-protein interactions, antibacterial and anticancer peptides. The lecture also reports on the determination of the three-dimensional structures of the macrocyclic peptide serving a mimetics of protein secondary structures. This includes a detailed NMR study (i.e., TOCSY, COSY, HSQC HMBC, and ROESY) combined with molecular dynamic simulation.
Speaker:
Daniel García Rivera — Full Professor, University of Havana (UH), Cuba.
How does Nature make small peptides conformationally fixed and metabolically stable? Among the many solutions, there are two of great incidences: cyclization and N-alkylation. The cyclization of peptides enables both to populate a biologically active conformation and to avoid the attack of exo-peptidases. Alternatively, N-alkylation introduces important features into small peptides, such as: enhanced flexibility and lipophilicity, endo-peptidase stability, and the possibility to reach otherwise highly strained conformations. For chemists, these processes are usually seen as separate synthetic operations that require ingenious strategies. However, there is one chemical process that enables to perform both cyclization and N-alkylation of peptides in one shot, i.e., the Ugi four-component reaction (Ugi-4CR). This is one-pot condensation of a primary amine, an oxo compound (i.e., ketone or aldehyde), a carboxylic acid, and an isocyanide to produce an N-substituted dipeptide backbone.
Participants: students, postgraduates and scientific-pedagogical workers of the faculty of Sciences of RUDN and other Universities.