Enzyme-assisted post-translational modifications (PTMs) constitute a major means of signaling across different cellular compartments. However, how non-enzymatic PTMs—despite their direct relevance to covalent drug development—impinge on cross-compartment signaling remains inaccessible as current target-ID technologies offer limited spatiotemporal resolution, and proximity mapping tools are also not guided by specific, biologically-relevant, ligand chemotypes. I will discuss how reimagining localised electrophile delivery concept has enabled us to establish a quantitative and direct profiling platform (Localis-rex) that ranks responsivity of compartmentalized sub-proteomes to non-enzymatic PTMs, and how application of this method has unveiled that even small fractions of endogenous proteins existing outside their canonical locale can show significantly-elevated electrophilic-metabolite sensing against the protein in its canonical locale. This minority of electrophile-sensing proteins can strongly influence activity of the bulk protein and hence cell decision making. .

Lighting the way: Function-guided proximity mapping & precision signaling interrogations open up new opportunities

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

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