Hijacking the cellular waste disposal system

Cells possess a natural pathway for disposing of proteins. Harnessing this pathway to degrade disease-causing proteins may have widespread use. A collaboration of US researchers has now identified how this could be done.

Identifying a strategy to degrade specific proteins within the cell would have massive therapeutic consequences.

According to new data overviewed in yesterdays edition of TherapeuticAdvances, a leading bulletin of cutting edge technology with pharmaceutical potential this may shortly be possible.

A collaboration of US research institutions has now met this challenge through the development of Protac technology. This represents a particularly novel strategy designed to target proteins to the ubiquitin pathway thereby harnessing the cell's natural protein degradation machinery.

To prove this concept, researchers focused on methionine aminopeptidase-2, a protein that covalently binds and deactivates ovalicin, an endogenous anti-angiogenenic protein.

A protac was engineered, fusing IkappaBalpha phosphopeptide at one end, which binds the ubiquitin complex, and ovalicin at the other end which binds MetAP-2. This chimera was able to target methionine aminopeptidase-2 to the ubiquitin complex resulting in its ubiquitination and degradation.

According to LeadDiscovery consultants "This particular strategy may offer a novel way of blocking angiogenesis, a vital component of tumor progression. More generally however, Protac technology could be conceivably used to target any intracellular protein if a corresponding molecule is identified or synthesized to which it binds". This exciting technology deserves industrial attention.

For information on in-depth analyses of this and related work visit the LeadDiscovery website at http://www.leaddiscovery.co.uk/target-discovery/therapeuticadvances.html.

LeadDiscovery is a leading Sussex based firm of drug discovery, development and commercialization consultants whose aim is to combine a background in the pharmaceutical industry with an internet platform to help academic and biotech based research groups to exploit their technology.