Research Projects

Peptides are crucial drug motifs due to their specificity in biological action, but their therapeutic application is limited due to their metabolic instability and conformational freedom. Several synthetic methodologies have been developed to modify peptides and proteins to enhance protein stability, control protein conformations, study protein-protein interactions, and improve pharmacological properties. The introduction of unnatural amino acids has been significant, but requires building blocks compatible with solid-phase peptide synthesis (SPPS) and targeted sequences. Late-stage functionalization (LSF) of peptides does not require specialized synthetic methods but requires excellent chemoselectivity under mild conditions. Site-selective modifications of aromatic residues, cysteine, lysine, C- and N-termini have been developed. In recent years, visible-light mediated radical coupling reactions have become pivotal for the construction of chemical bonds due to their growth in photochemistry. Primary amines, abundant in nature with diverse chemical structures, can be used as starting materials for the generation of alkyl radicals via a deamination process. The identification of new ideas for the formation of C-X and C-C bonds through deamination processes is an emerging trend in chemistry, offering retrosynthetic and late-stage functionalization of complex molecules. This study aims to generate visible-light induced, photocatalyst or photo-absorbing EDA complexes mediated cleavage of pyridinium C-N bond to produce chemically modified peptides and proteins through the formation of C(sp)-C(sp3), C(sp2)-C(sp3), C(sp3)-C(sp3), and bond formation reactions.