Method for thiolation and covalent conjugation of target protein

Persulfidation is a unique posttranslational protein modification that protects our cells and proteomes against oxidative stress and ageing. Very recent work from the Malopolska Centre of Biotechnology (Jagiellonian University in Krakow) shows that this small chemical modification is installed by a cellular protein, called Ubiquitin related modifier 1 (Urm1). Not only, is the pathway activated during oxidative stress, but it is also surprisingly linked to another type of protein modification. The study provides new molecular insights into a previously unrecognized cellular mechanism and indicates that Urm1-based therapeutics could play a significant role in decelerating ageing.

In detail, the study shows that the action of Urm1 is able to protect other enzymes under oxidative stress. Urm1, previously known to incorporate sulfur into transfer RNA (tRNA), is also able to deliver sulfur atoms to specific target proteins. This process, called persulfidation, is an evolutionarily conserved constitutive defence mechanism against oxidative stress that is critical during ageing.

Possible applications of the technology:

1. to attach macromolecular labels (e.g. fluorescence proteins, affinity tags, barcode sequences) covalently to purified proteins or cell extracts
2. as a sensor for oxidative conditions in aqueous solutions and more heterogenous biological systems (e.g. serum, cell lysates, cultures)
3. in chemoenzymatic semi synthesis of proteins where an expression of synthetically produced protein can be ligated with a peptide of interest
4. reengineering of any existing protein tag to covalently link to protein of interest
5. reengineering of existing biomarkers with thiocarboxylate to form stable interaction
6. in biorthogonal chemistry to selectively track oxidation/ persulfidation states of peroxidatic/catalytic cysteines in vivo.

Current development status

Experimental technologies

Desired business relationship

Technology selling

Patent licensing