With CliCr® as our proprietary platforms, we offer a powerful copper free click chemistry reagent for the life science industry. The platform is based on TMTHSI, a 7-membered ring.
Read more about our platform or contact us today at info@cristaltherapeutics.com.
The advantages of CliCr® compared to other copper-free click reagents
Shorter reaction times than all other marketed copper-free click reagents, providing greater chemical yield and enabling reactions with and towards highly labile molecules.
Highly stable reagents yielding stable, irreversibly linked products.
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 at info@cristaltherapeutics.com in case of any sort of enquiry.
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.
Generation of bioconjugate-based therapeutics, including antibody-drug conjugates, ligand-drug conjugates or targeted nanoparticles.
Efficient and precise labelling of a wide variety of molecules for use in research or for the generation of diagnostics.
Efficient and high quality synthesis of complex molecules, e.g. for compound libraries or for polymer synthesis.
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.
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.
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.
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.
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 (Y-axis, as in Click Chemistry Brochure on https://www.iris-biotech.de/click-chemistry). 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 (X-axis), facilitating a better water solubility, these characteristics contribute to the superiority of TMTHSI as a new click reagent.
Publication
Specific N-terminal attachment of TMTHSI linkers to native peptides and proteins for strain-promoted azide alkyne cycloaddition, Timmers et al, ChemComm 2023, https://doi.org/10.1039/D3CC03397J
Versatile click linker enabling native peptide release from nanocarriers upon redox trigger, Hebels et al, Bioconjugate chemistry 2023, https://doi.org/10.1021/acs.bioconjchem.3c00484
Orthogonal covalent entrapment of cargo into biodegradable polymeric micelles via Native Chemical Ligation, Hebels et al, Biomacromolecules 2023 https://doi.org/10.1021/acs.biomac.2c00865
Exploring the chemical properties and medicinal applications of tetramethylthiocycloheptyne sulfoximine used in Strain-Promoted Azide–Alkyne Cycloaddition reactions, Timmers et al, Pharmaceuticals 2023, https://doi.org/10.3390/ph16081155
TMTHSI, a superior 7-membered ring alkyne containing reagent for strain-promoted azide–alkyne cycloaddition reactions, Weterings et al, Chemical Sciences 2020, 11, p 9011-9016. https://doi.org/10.1039/D0SC03477K
We are interested in exploring strategic collaborations utilising CliCr® to generate novel and superior conjugate products, for either diagnostic or therapeutic applications.
Please send an e-mail to info@cristaltherapeutics.com.
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