Copper Free Click Chemistry Linkers

Copper free click chemistry linkers have been widely used for in vivo bioconjugation applications. Conventional “Click Chemistry” requires the presence of cytotoxic of Cu(I) catalyst, which limits its applications in biological systems. The Copper-free Click Chemistry is based on the reaction of a cyclooctyne (DBCO and BCN click chemistry) moiety with an azide-labeled reaction partner, known as strain-promoted alkyne azide cycloaddition (SPAAC).

This new “Click Chemistry” is very fast at room temperature and does not require a cytotoxic Cu(I) catalyst. As a result, the copper free click chemistry has been advanced in molecular imaging and drug delivery for diagnosis and therapy.

BCN PEG Maleimide

BCN PEG maleimie linkers bear a click chemistry BCN group and a thiol reactive maleimide functional group. These heterofunctional crosslinkers have added hydrophilicity from the PEG spacer.

While the BCN groups react specifically with azide groups, the maleimides react readily with thiol groups on biomolecules. The linkers are ideal for site specific conjugations where thiol and azide groups are present.

Cyclopropene Linkers

Cyclopropenes are the smallest unsaturated carbocyclic compounds with high strain energy. It is highly reactive in additions, cycloadditions and ring opening reactions. These mimimalist carocylic compounds have witnessed a significant advancement in affinity-based protein labeling and synthesis of photo-cross-linkers suitable for live-cell imaging.

DBCO Linkers

DBCO Linkers can undergo copper free click chemistry Reaction via a strain-promoted 1,3-dipolar cycloaddition of cyclooctynes and azides. The spontaneously conjugation with azide-modified biomolecules without the need for toxic Cu catalysts makes the DBCO reagents ideal for living cells and organisms study.

DBCO PEG NHS

DBCO PEG NHS linkers have popular copper free click chemistry DBCO moiety on one end and an active NHS ester group on the other.

The NHS ester functional group is widely used to conjugate the crosslinker with biomolecules with amino functional group. The resulting biomolecule bearing DBCO functional group can undergo a click chemistry with biomolecules bearing azide group. The process has no toxic metal catalyst involved and is fast and high yielding

PEG spacers add enhanced aqueous solubility and make the crosslinkers suitable for in vivo bioconjugation applications.

TCO Linkers

TCO Linkers are bioorthogonal agents for tetrazine. The cycloaddition reaction between tetrazine and trans-cyclooctene (TCO) is rapidly growing in use for bioconjugation, molecular imaging and cell-based diagnostics.

Aminooxy-PEG-TCO

Aminooxy PEG TCO linkers have an aminooxy moiety on one end and a TCO group on the other. The aminooxy group readily reacts with aldehyde groups of biomolecules. The TCO group on the other end reacts with tetrazine group in a ultrafast and highly specific fashion.

Linkers with aminooxy and TCO combination are ideal for ADC conjugation of sugar modified biomolecules.
crosslinkers suitable for in vivo bioconjugation applications.

TCO PEG NHS

TCO PEG NHS linkers have TCO moiety on one end that can undergo biorthogonal reaction with tetrazine modified biomolecules. At meantime, the NHS ester functional group on the other end provides opportunity for conjugation with molecules bearing amine groups in a fast and efficient fashion.

Although both reactions are fast and high yielding, they don’t interfere with each other. Therefore, TCO PEG NHS spacer can be used in a consecutive or a simultaneous way for bioconjugations.

Tetrazine Linkers

Tetrazine Linkers – Bio-orthogonal ligation tools for TCO and Cyclopropene: Tetrazine linkers are chemoselective and specifically react with trans-cyclooctene (TCO). The ultrafast kinetics offer researchers ideal tools for their research in bioconjugation, cell engineering and site/target specific conjugations.