Source 1primary paper2020Science Advances
Toolkit/opto-PROTAC
opto-PROTAC
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
opto-PROTAC is a light-inducible PROTAC design in which a photolabile caging group is installed on pomalidomide-based degraders to block activity in the dark and permit target protein degradation after ultraviolet A irradiation. It was demonstrated using caged pomalidomide and the PROTACs dBET1 and dALK to achieve spatiotemporal control of protein destruction.
Usefulness & Problems
Why this is useful
This design provides optical control over targeted protein degradation, allowing degradation to be restricted to defined times and illuminated regions. It is useful when constitutive PROTAC activity in the dark would reduce experimental precision or prevent localized perturbation.
Source:
to enable the degradation of protein targets in a spatiotemporal manner
Problem solved
opto-PROTAC addresses the problem of poor temporal and spatial control in conventional PROTAC-mediated protein degradation. By suppressing degrader activity until ultraviolet A exposure, it enables inducible and spatially restricted target destruction.
Problem links
Need conditional protein clearance
Derivedopto-PROTAC is a light-inducible PROTAC design in which a photolabile caging group is installed on pomalidomide-based degraders to suppress activity in the dark and enable protein degradation after ultraviolet A irradiation. It was reported to confer spatiotemporal control of target protein destruction and was demonstrated on caged pomalidomide, dBET1, and dALK.
Need precise spatiotemporal control with light input
Derivedopto-PROTAC is a light-inducible PROTAC design in which a photolabile caging group is installed on pomalidomide-based degraders to suppress activity in the dark and enable protein degradation after ultraviolet A irradiation. It was reported to confer spatiotemporal control of target protein destruction and was demonstrated on caged pomalidomide, dBET1, and dALK.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Mechanisms
Degradationphotocagingphotocagingphotodecagingphotodecagingtargeted protein degradationtargeted protein degradationTechniques
No technique tags yet.
Target processes
degradationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: actuatoroperating role: regulator
The design strategy involves installation of a photolabile caging group on pomalidomide and on pomalidomide-based PROTACs such as dBET1 and dALK. Activation requires ultraviolet A irradiation, and the caged compounds are reported to remain inactive in the dark until light exposure removes the block on degradation activity.
The available evidence is limited to a single source report and does not establish independent replication. The summary evidence specifies ultraviolet A as the activating input, but does not provide detailed information here on photochemical efficiency, depth of tissue applicability, or performance across diverse targets and biological systems.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
activity state in dark no activities
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
Approval Evidence
1 source5 linked approval claimsfirst-pass slug opto-protac
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
Source:
activity state controlsupports
These opto-PROTACs have no activity in the dark and can induce restricted degradation upon ultraviolet A irradiation.
These opto-PROTACs display no activities in the dark, while the restricted degradation can be induced at a specific time and rate by ultraviolet A irradiation.
Source:
design strategysupports
Light-inducible protein degradation was demonstrated by adding a photolabile caging group on pomalidomide and on the PROTACs dBET1 and dALK.
By adding a photolabile caging group on pomalidomide as a parental compound and two additional PROTACs, dBET1 and dALK, we demonstrated light-inducible protein degradation.
Source:
functional capabilitysupports
Opto-PROTAC enables degradation of protein targets in a spatiotemporal manner.
to enable the degradation of protein targets in a spatiotemporal manner
Source:
generalizabilitysupports
The approach is presented as a generalizable platform for development of light-controlled PROTACs.
Our approach provides a generalizable platform for the development of light-controlled PROTACs
Source:
introduction of toolsupports
The authors introduce a light-inducible switch on PROTACs termed opto-PROTAC.
Here, we introduce a light-inducible switch on PROTACs, thereafter termed as opto-PROTAC
Source:
Comparisons
Source-backed strengths
The reported opto-PROTACs showed no activity in the dark and induced restricted degradation upon ultraviolet A irradiation. The approach was demonstrated across multiple pomalidomide-based molecules, including caged pomalidomide, dBET1, and dALK, supporting its use as a general light-inducible switch on this degrader class.
Compared with GFP-CRY2
opto-PROTAC and GFP-CRY2 address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation; same primary input modality: light
Compared with pc-PROTAC1
opto-PROTAC and pc-PROTAC1 address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation, photocaging, targeted protein degradation; same primary input modality: light
Compared with photo-caged PROTACs
opto-PROTAC and photo-caged PROTACs address a similar problem space because they share degradation.
Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation, targeted protein degradation; same primary input modality: light
Ranked Citations
- 1.