The bioconjugation of proteins with chemically relevant molecular probes mimic nature’s ability to selectively modify proteins and can directly improve the human condition. Therefore, the aim of this research is to develop new, chemically distinct, reagents for selective protein modification. Molecular probes able to undergo photo-induced bioconjugation are of particular interest as photochemical reactions allow for spatiotemporal control over reactivity. We consider a means to achieve an effective photo-bioconjugation process by utilizing the photolability of tryptophan (Trp). Being the most photolabile of all the naturally occurring amino acids coupled with its low-abundance, makes Trp an ideal candidate for bioconjugation. We report the synthesis of a variety of N-carbamoyl pyridinium salts that, upon irradiation with UV-B light, have shown complete tryptophan selectivity over other redox active or photo-labile amino acid, verified via Tandem MS, in a range of protein and peptides of varying structural complexity. Furthermore, modified Trp containing biomolecules have been isolated confirming the location of the labelling group to be at the C2 position of the indole. The reaction has been demonstrated to be a viable mode for selectively modifying Trp as high conversions has been achieved at varying biomolecule concentrations, in completely aqueous media, in short reaction times, and is aided by the addition of glutathione.

Synthesis of molecular probes for the selective modification of tryptophan residues in peptides and proteins

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.