Strategies for modification of tryptophan residues: recent advances and future perspectives in photo-/ electrochemical-induction, and metal catalysis

Abstract

Recent advancements in tryptophan (Trp) modification have greatly expanded its applications across drug discovery, materials science, and environmental monitoring. Trp, an essential amino acid with a unique indole ring, serves as an ideal target for chemical modification due to its redox-active nature. Photo- and electrochemical methods, which utilize light and electric energy, respectively, offer precise, efficient, and environmentally friendly approaches for Trp modification. Photochemical-induced transformations improve Trp's optical properties, such as fluorescence, enhancing its utility in bioimaging and sensor applications, while also introducing bioactive functional groups. Electrochemical modifications enable controlled oxidation and reduction, facilitating the selective addition of functional groups like hydroxyl or amino groups, essential for synthesizing Trp derivatives aimed at protein modulation. Additionally, metal-catalyzed reactions using transition metals such as palladium or copper enable site-selective modifications through C-H activation and cross-coupling, creating Trp derivatives with enhanced properties for optoelectronic and biomedical applications. These advancements highlight the potential of Trp-based bioconjugation strategies across diverse scientific disciplines.