Source 1primary paper2020Molecules
Toolkit/alkynyl-functionalized photocleavable linker
alkynyl-functionalized photocleavable linker
Also known as: ethynyl function on the photocleavable linker
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The alkynyl-functionalized photocleavable linker is a construct pattern used in caged antisense morpholino reagents, in which an ethynyl-bearing photocleavable linker is coupled to an oligonucleotide. In the caged state it inhibits DNA binding, and brief 405-nm illumination restores antisense activity through linker photocleavage.
Usefulness & Problems
Why this is useful
This design enables light-triggered control of antisense morpholino function, allowing gene function to be modulated with spatial and temporal precision in vivo. The ethynyl-functionalized linker also facilitates synthetic assembly by enabling coupling through a Huisgen 1,3-dipolar cycloaddition.
Problem solved
This construct addresses the need to keep antisense morpholino activity inactive until a defined light stimulus is applied. It also addresses preparation challenges in ccMO synthesis by introducing an ethynyl function on the photocleavable linker to expedite coupling to the oligonucleotide.
Problem links
Need precise spatiotemporal control with light input
DerivedThe alkynyl-functionalized photocleavable linker is a construct pattern used in caged antisense morpholino reagents, in which an ethynyl-bearing photocleavable linker is coupled to an oligonucleotide. In the caged state it inhibits DNA binding, and brief 405-nm illumination restores antisense activity through linker photocleavage.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Mechanisms
PhotocleavageTechniques
Computational DesignTarget processes
No target processes tagged yet.
Input: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: actuatorswitch architecture: cleavage
The linker contains an ethynyl function specifically introduced to enable Huisgen 1,3-dipolar cycloaddition for coupling with the oligonucleotide. Functional activation requires brief 405-nm light exposure, and the construct is described in the context of caged antisense morpholino reagents.
The supplied evidence is limited to a single 2020 source and does not provide quantitative performance metrics such as uncaging efficiency, dynamic range, or kinetics. The evidence also does not specify organismal validation details, off-target effects, or how broadly the design has been benchmarked against alternative caging strategies.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.
HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.
HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.
HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.
HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.
HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.
HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.
HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.
Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.
Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.
Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.
Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.
Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.
Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.
Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Approval Evidence
1 source2 linked approval claimsfirst-pass slug alkynyl-functionalized-photocleavable-linker
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide.
Source:
design improvementsupports
The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.
We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Source:
synthetic advantagesupports
Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.
The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Source:
Comparisons
Source-backed strengths
Source literature reports that the caging strategy inhibits DNA binding ability and that activity can be restored by brief illumination with 405-nm light. The reported ccMO design is described as expediting synthetic preparation and overcoming many preparation challenges, while being presented as an excellent tool for in vivo gene-function modulation.
Compared with Opto-Casp8-V1
alkynyl-functionalized photocleavable linker and Opto-Casp8-V1 address a similar problem space.
Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light
Compared with Opto-Casp8-V2
alkynyl-functionalized photocleavable linker and Opto-Casp8-V2 address a similar problem space.
Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light
alkynyl-functionalized photocleavable linker and randomly attached cage compounds on silencing oligonucleotides address a similar problem space.
Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light
Ranked Citations
- 1.