Source 1primary paper2019Journal of the American Chemical Society
Toolkit/photo-caged PROTACs
photo-caged PROTACs
Also known as: pc-PROTACs
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Photo-caged PROTACs (pc-PROTACs) are light-activated proteolysis-targeting chimeras designed to trigger targeted protein degradation only after irradiation. The reported study presented pc-PROTACs as a general strategy for inducing degradation activity with light and showed that pc-PROTAC1 was potently active in live cells only after light exposure.
Usefulness & Problems
Why this is useful
pc-PROTACs are useful for imposing optical control over PROTAC-mediated protein degradation, enabling degradation activity to be switched on with light rather than being constitutively active. This addresses the need for conditional activation of targeted protein degradation in live-cell settings.
Source:
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Problem solved
This tool helps solve the problem of how to induce protein degradation in a light-dependent manner. The cited work specifically established a strategy for activating PROTAC degradation activity only after irradiation.
Problem links
Need conditional protein clearance
DerivedPhoto-caged PROTACs (pc-PROTACs) are light-activated proteolysis-targeting chimeras designed to induce protein degradation only after irradiation. The reported study established this as a general strategy and applied it to at least one additional target, BTK, through construction of pc-PROTAC3.
Need precise spatiotemporal control with light input
DerivedPhoto-caged PROTACs (pc-PROTACs) are light-activated proteolysis-targeting chimeras designed to induce protein degradation only after irradiation. The reported study established this as a general strategy and applied it to at least one additional target, BTK, through construction of pc-PROTAC3.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Mechanisms
Degradationlight-triggered activationlight-triggered activationphotocaging/photodeprotectionphotocaging/photodeprotectiontargeted 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
Implementation requires a PROTAC rendered inactive by a photocaging strategy and subsequent light irradiation to activate degradation. The provided evidence confirms live-cell use but does not provide construct chemistry, illumination parameters, or delivery details.
The supplied evidence does not specify the photocaging group, irradiation wavelength, E3 ligase ligand, target protein panel, or quantitative degradation performance. Independent replication and validation breadth beyond the originating study are not documented in the provided material.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation.
the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.
this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Approval Evidence
1 source3 linked approval claimsfirst-pass slug photo-caged-protacs
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Source:
capabilitysupports
Photo-caged PROTACs can induce protein degradation activity with light.
Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light.
Source:
generalizabilitysupports
The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.
this approach was successfully applied to construct pc-PROTAC3 of BTK
Source:
general strategysupports
A general strategy to induce protein degradation with light was established.
Thus, a general strategy to induce protein degradation with light was established
Source:
Comparisons
Source-backed strengths
The available evidence shows that pc-PROTACs can induce degradation activity with light and that pc-PROTAC1 displayed potent degradation activity in live cells only after irradiation. The study also described the approach as a general strategy rather than a single isolated construct.
Compared with GFP-CRY2
photo-caged PROTACs 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
photo-caged PROTACs 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, light-triggered activation, targeted protein degradation; same primary input modality: light
Compared with TRIM21-nanobody chimeras
photo-caged PROTACs and TRIM21-nanobody chimeras 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.