Cleavable Crosslinkers for Oligonucleotide Conjugation

Precision Linkers Designed for Controlled Release, Biological Targeting & Functional Studies

Cleavable crosslinkers enable covalent attachment of oligonucleotides to other biomolecules—with the ability to release the cargo or trigger dissociation under specific conditions.

At Bio-Synthesis, we offer a comprehensive suite of cleavable linker chemistries tailored for advanced bioconjugation, imaging, therapeutic delivery, and structural biology applications.

What Are Cleavable Crosslinkers?
Cleavable crosslinkers are chemical linkers with two reactive ends and an internally cleavable bond. They enable temporary linkage between oligos and:

• Protein such as Enzyme, Antibody
• Peptides
• Nanoparticles
• Drugs and small molecules

The linkage is designed to break under specific triggers such as pH, light, redox conditions, or enzymatic activity.

Types of Cleavable Linkers We Offer

Product	Cleavable Type	Cleaved By	Typical Applications
Thiol-C6 S-S	Disulfide Linker (–S–S–)	Reducing agents (e.g., GSH, DTT); redox-cleavable, responsive to intracellular reducing agents	Antibody-oligo conjugates, intracellular release
SPDP	Disulfide Linker (–S–S–)	Cleaved by intracellular glutathione	Antibody-oligo conjugates, intracellular release
Sulfo-LC-SPDP	Disulfide Linker (–S–S–)	Water-soluble variant	Antibody-oligo conjugates, intracellular release
Hydrazone	Acid-Labile	Cleaved in endosomal acidic pH; used in ADCs	Targeted delivery systems
Mal-PEG4-Val-Cit-PAB-PNA	Enzyme-Cleavable	Cleaved by cathepsin B	ADC oligo conjugates
Mc-Val-Cit-PABC-PNP	Enzyme-Cleavable	Cleaved by cathepsin B	ADC oligo conjugates
Mal_PEG1-Val-Cit-PAB-PNP	Enzyme-Cleavable	Cleaved by cathepsin B	ADC oligo conjugates
Gly-Phe-Leu-Gly (GFLG)	Enzyme-Cleavable	Cleaved by lysosomal enzymes	ADC oligo conjugates
Mal-Amide-PEG4-Val-cit-PAB-PNP	Enzyme-Cleavable	Cleaved by cathepsin B	ADC oligo conjugates
PC Spacer	Photo-cleavable	Cleavable wavelength: ~365 nm; useful in solid-phase synthesis or drug release	Light-controlled hybridization/release
PC Linker	Photo-cleavable	—	Light-controlled hybridization/release
PC-Biotin	Photo-cleavable	Cleavable wavelength: ~365 nm; affinity purification and light-induced release	Light-controlled hybridization/release
PC Amino C6-Modifier	Photo-cleavable	PC Amino-Modifier is a photocleavable C6 amino-modifier	Light-controlled hybridization/release
Azobenzene	Photo-cleavable	—	Light-controlled hybridization/release
NPOM Caged-dT	Photo-cleavable	Cleavable wavelength: ~365 nm; controls hybridization or transcription	Light-controlled hybridization/release
DEACM Caged-dG	Photo-cleavable	Allows spatial-temporal control of biological processes	Light-controlled hybridization/release
4-Thio-dU	Photo-cleavable	—	Light-controlled hybridization/release
2-Aminopurine	Photo-cleavable	—	Light-controlled hybridization/release
6-Thio-dG	Photo-cleavable	—	Light-controlled hybridization/release
2-thio-dT	Photo-cleavable	—	Light-controlled hybridization/release
3-Cyanovinylcarbazole (CNVK)	Photo-cleavable	—	Light-controlled hybridization/release
Azobenzene derivatives	Thermally-cleavable	Heat-sensitive scission	Thermally triggered hybridization/release

Need a specific linker not listed above? Contact us for custom synthesis options.

Applications of Cleavable Oligo Crosslinkers

• Controlled drug or payload release
• Photocleavable nucleic acid delivery systems
• Biomolecule mapping and interaction studies
• Affinity purification and elution
• Triggered in vivo targeting and clearance
• Responsive biosensors or nanodevices

Available Formats

• 5′, 3′, or internal linker insertion
• Conjugation to DNA, RNA, modified bases, or non-nucleic scaffolds
• Spacer-arm variants (e.g., PEG, alkyl chains) available
• Dual-cleavable and cleavable + fluorescent systems offered

Get a Custom Quote
Need a cleavable linker strategy for your oligo-drug conjugate or sensor system?

Email: info@biosyn.com
Request a consultation with our conjugation chemistry team.