CliCr^®

Our copper free click chemistry reagent

With CliCr^® as one of our proprietary platforms, we offer a powerful copper free click chemistry reagent for the life science industry. The platform is based on TMTHSI.

Advantages of our copper free click technology

The advantages of CliCr^® compared to other copper-free click reagents

Faster click reactions

Shorter reaction times than all other marketed copper-free click reagents, providing greater chemical yield and enabling reactions with and towards highly labile molecules.

Generation of stable (bio)conjugates

Highly stable reagents yielding stable, irreversibly linked products.

Greater variety of click reactions

Due to a large variation of linkers that can easily be attached to the seven-membered ring.

We use attractive business models to allow for both early stage development exploration up to applications in actual products. Please contact us in case of any sort of enquiry.

Potential CliCr^®applications

The versatility of ligand attachment to linking moieties has been illustrated by reaction of TMTHSI-derivatives of the CliCr^® platform with small molecules, exemplified by the click-reaction with a dye and a folic acid derivative, as well as peptide and nucleic acid biologics. The resulting biomolecular constructs were among others attached to CriPec^® nanoparticles.

Therapeutic bioconjugates

Generation of bioconjugate-based therapeutics, including antibody-drug conjugates, ligand-drug conjugates or targeted nanoparticles.

Label conjugation

Efficient and precise labelling of a wide variety of molecules for use in research or for the generation of diagnostics.

Synthesis

Efficient and high quality synthesis of complex molecules, e.g. for compound libraries or for polymer synthesis.

Combining the CriPec^® technology with the CliCr^® platform

A plethora of additional important applications in biochemical, aqueous environments is envisioned, such as the construction of antibody drug conjugates (ADC’s), Surface Plasmon Resonance (SPR) applications and conjugation of chelator moieties for radio-active isotope incorporation in theragnostic applications. This will be expanded to biological applications in cell lysates, in tissue culture and beyond by combining the CriPec^® technology with the CliCr^® platform towards the synthetic vaccine platform CriVac^®.

The smaller hydrophobic size of TMTHSI, will lead to a smaller “observer effect” with less influence on the activity of the clicked ligand in addition to causing less protein binding.

Improved copper free SPAAC reagents

We have developed a compelling, alternative ‘click’ reagent containing a strained triple bond that does not require copper catalysis. These reagents are used in strain-promoted azide-alkyne cycloaddition reactions (SPAACs) and are essential for applications in the biological sciences.

Meeting the demands of the life science industry

Many SPAAC reagents are hydrophobic, show slow conversion, are incompatible with biomolecules or are too unstable. CliCr^® overcomes these disadvantages, and meets with all demands as required in the life science industry, by the innovative TMTHSI moiety. Upon derivatisation of TMTHSI with a broad range of potential linkers, the proprietary CliCr^® platform with superior SPAAC reagents is generated.

Combining high reactivity with water solubility

Upon evaluation of the kinetics, the reaction rate of benzyl azide and TMTHSI was determined to be 0.8 M^-1s^-1. The obtained k value of BCN-OH was 0.14 M^-1s^-1. This reaction rate observed by MS showed that TMTHSI is one of the most reactive available click reagents. It is > 5 fold more reactive than BCN and 2.5 fold more reactive than DBCO. It has a similar reactivity to BARAC but is a less sterically bulky alkyne-containing reagent for strain-promoted azide-alkyne cycloaddition reactions.

Together with the experimentally determined low logP, facilitating a better water solubility, these characteristics contribute to the superiority of TMTHSI as a new click reagent.

Publication

TMTHSI, a superior 7-membered ring alkyne containing reagent for strain-promoted azide–alkyne cycloaddition reactions, Jimmy Weterings, Cristianne J. F. Rijcken, Harald Veldhuis, Tommi Meulemans, Darya Hadavi, Matt Timmers, Maarten Honing, Hans Ippel and Rob M. J. Liskamp, Chemical Sciences 2020, 11, p 9011-9016. https://doi.org/10.1039/D0SC03477K

Request for a quotation or more information about CliCr^®

We are interested in exploring strategic collaborations utilising CliCr^® to generate novel and superior conjugate products.

Please leave your details here or send an e-mail to clicr@cristaltherapeutics.com.

CliCr®