[HTML][HTML] Inducible degradation of target proteins through a tractable affinity-directed protein missile system
LM Simpson, TJ Macartney, A Nardin, LJ Fulcher… - Cell Chemical …, 2020 - cell.com
The affinity-directed protein missile (AdPROM) system utilizes specific polypeptide binders
of intracellular proteins of interest (POIs) conjugated to an E3 ubiquitin ligase moiety to
enable targeted proteolysis of the POI. However, a chemically tuneable AdPROM system is
more desirable. Here, we use Halo-tag/VHL-recruiting proteolysis-targeting chimera
(HaloPROTAC) technology to develop a ligand-inducible AdPROM (L-AdPROM) system.
When we express an L-AdPROM construct consisting of an anti-GFP nanobody conjugated …
of intracellular proteins of interest (POIs) conjugated to an E3 ubiquitin ligase moiety to
enable targeted proteolysis of the POI. However, a chemically tuneable AdPROM system is
more desirable. Here, we use Halo-tag/VHL-recruiting proteolysis-targeting chimera
(HaloPROTAC) technology to develop a ligand-inducible AdPROM (L-AdPROM) system.
When we express an L-AdPROM construct consisting of an anti-GFP nanobody conjugated …
Inducible Degradation of Target Proteins Through a Tractable Affinity-Directed PROtein Missile (AdPROM) System
L Simpson, T Macartney, A Nardin… - Available at SSRN …, 2020 - papers.ssrn.com
Previously we described an Affinity-directed PROtein Missile (AdPROM) system that utilises
specific polypeptide binders of intracellular proteins of interest (POIs) conjugated to an E3
ubiquitin ligase moiety to enable targeted proteolysis of the POI. However, a chemically
tuneable AdPROM system is more desirable. Here, we combined Halo/VHL-recruiting
proteolysis-targeting chimeras (HaloPROTACs) with AdPROM for ligand-inducible (L-
AdPROM) degradation of POIs. For POIs, cells were generated in which ULK1, FAM83D or …
specific polypeptide binders of intracellular proteins of interest (POIs) conjugated to an E3
ubiquitin ligase moiety to enable targeted proteolysis of the POI. However, a chemically
tuneable AdPROM system is more desirable. Here, we combined Halo/VHL-recruiting
proteolysis-targeting chimeras (HaloPROTACs) with AdPROM for ligand-inducible (L-
AdPROM) degradation of POIs. For POIs, cells were generated in which ULK1, FAM83D or …
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