ArticleResearch square2026
RuPHOTACs Provide Photocontrol Over Protein Degradation with Optimized Properties for Biological Applications.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
6 authors.
Funding
Abstract
PROteolysis TArgeting Chimeras (PROTACs) are bifunctional molecules that catalyze degradation of selected proteins by inducing protein:protein interactions (PPIs) between E3 ubiquitin ligases and the protein of interest. A critical limitation is undesired effects in untargeted tissues, necessitating approaches to impose spatiotemporal control over PROTAC function. Here we present Ru(II) photocages that can be released with low energy light, providing triggered PROTAC activity on demand. The systems, termed Ruthenium-based PHOToActivated Chimeras (RuPHOTACs), were validated by targeting bromodomain-containing proteins, which act as crucial epigenetic regulators, and also strongly reduced levels of c-MYC and PIM1. The novel RuPHOTACs demonstrate that the incorporation of metal components within organic PROTACs confers multiple advantages for light-controlled systems for chemical biology applications, including the highest selectivity for activation in the light vs. the dark, improved potency against the target proteins of interest, and increased efficacy
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