Chemical modification

pChem is a computational tool that provides a pipeline for performance assessment of chemoproteomic probes, with the ability to score the profiling efficiency, modification homogeneity and proteome-wide residue selectivity of a tested probe.

Developing stimuli-responsive bioorthogonal tetrazine ligations remains highly challenging, but a versatile approach that uses photocaged dihydrotetrazines has now been developed. Photouncaging results in the spontaneous formation of reactive tetrazines that rapidly react with dienophiles such as trans-cyclooctenes. As a demonstration, the method was used for live-cell labelling with single-cell precision and light-triggered drug delivery.

Analogues of mRNA 5′ caps containing a photo-cleavable group have now been developed. These so-called FlashCaps can be used for routine in vitro transcription to make long mRNAs containing a cap. In cells, the capped mRNAs are translationally muted; however, upon irradiation by light, the photo-cleavable group is removed without leaving any remaining modification and mRNA is then translated into the corresponding protein.

Using isocyanic acid as a CO₂ analog generates a stable mimic of lysine carboxylation, enabling development of a quantitative chemoproteomic approach to identify this modification in proteins and explore the lysine carboxylome of a cyanobacterium.