Toolkit/photo-caged PROTACs

photo-caged PROTACs

Construct Pattern·Research·Since 2019

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

Derived

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.

Need precise spatiotemporal control with light input

Derived

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.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Architecture: A reusable architecture pattern for arranging parts into an engineered system.

Techniques

No technique tags yet.

Target processes

degradation

Input: Light

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating 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

Claim 1capabilitysupports2019Source 1needs review

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.
Claim 2capabilitysupports2019Source 1needs review

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.
Claim 3capabilitysupports2019Source 1needs review

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.
Claim 4capabilitysupports2019Source 1needs review

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.
Claim 5capabilitysupports2019Source 1needs review

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.
Claim 6capabilitysupports2019Source 1needs review

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.
Claim 7capabilitysupports2019Source 1needs review

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.
Claim 8conditional activitysupports2019Source 1needs review

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
Claim 9conditional activitysupports2019Source 1needs review

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
Claim 10conditional activitysupports2019Source 1needs review

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
Claim 11conditional activitysupports2019Source 1needs review

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
Claim 12conditional activitysupports2019Source 1needs review

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
Claim 13conditional activitysupports2019Source 1needs review

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
Claim 14conditional activitysupports2019Source 1needs review

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
Claim 15generalizabilitysupports2019Source 1needs review

The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.

this approach was successfully applied to construct pc-PROTAC3 of BTK
Claim 16generalizabilitysupports2019Source 1needs review

The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.

this approach was successfully applied to construct pc-PROTAC3 of BTK
Claim 17generalizabilitysupports2019Source 1needs review

The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.

this approach was successfully applied to construct pc-PROTAC3 of BTK
Claim 18generalizabilitysupports2019Source 1needs review

The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.

this approach was successfully applied to construct pc-PROTAC3 of BTK
Claim 19generalizabilitysupports2019Source 1needs review

The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.

this approach was successfully applied to construct pc-PROTAC3 of BTK
Claim 20generalizabilitysupports2019Source 1needs review

The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.

this approach was successfully applied to construct pc-PROTAC3 of BTK
Claim 21generalizabilitysupports2019Source 1needs review

The photocaged PROTAC approach was successfully applied to construct pc-PROTAC3 of BTK.

this approach was successfully applied to construct pc-PROTAC3 of BTK
Claim 22general strategysupports2019Source 1needs review

A general strategy to induce protein degradation with light was established.

Thus, a general strategy to induce protein degradation with light was established
Claim 23general strategysupports2019Source 1needs review

A general strategy to induce protein degradation with light was established.

Thus, a general strategy to induce protein degradation with light was established
Claim 24general strategysupports2019Source 1needs review

A general strategy to induce protein degradation with light was established.

Thus, a general strategy to induce protein degradation with light was established
Claim 25general strategysupports2019Source 1needs review

A general strategy to induce protein degradation with light was established.

Thus, a general strategy to induce protein degradation with light was established
Claim 26general strategysupports2019Source 1needs review

A general strategy to induce protein degradation with light was established.

Thus, a general strategy to induce protein degradation with light was established
Claim 27general strategysupports2019Source 1needs review

A general strategy to induce protein degradation with light was established.

Thus, a general strategy to induce protein degradation with light was established
Claim 28general strategysupports2019Source 1needs review

A general strategy to induce protein degradation with light was established.

Thus, a general strategy to induce protein degradation with light was established
Claim 29targeted degradationsupports2019Source 1needs review

pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.

this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Claim 30targeted degradationsupports2019Source 1needs review

pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.

this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Claim 31targeted degradationsupports2019Source 1needs review

pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.

this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Claim 32targeted degradationsupports2019Source 1needs review

pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.

this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Claim 33targeted degradationsupports2019Source 1needs review

pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.

this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Claim 34targeted degradationsupports2019Source 1needs review

pc-PROTAC1 efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish.

this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish
Claim 35targeted degradationsupports2019Source 1needs review

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 lyso-ArchT

photo-caged PROTACs and lyso-ArchT 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 lyso-ChR2

photo-caged PROTACs and lyso-ChR2 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

Ranked Citations

  1. 1.
    StructuralSource 1Journal of the American Chemical Society2019Claim 1Claim 2Claim 3

    Extracted from this source document.