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1-(Aminomethyl)-Trans-Cyclooct-4-Ene, a New TCO Derivative for Target Visualization and Target Engagement Measurement in Cells

submitted on 01.11.2020, 12:16 and posted on 03.11.2020, 05:30 by Cécile Echalier, Anna Rutkowska, Douglas W. Thomson, Lee Edwards, Blandine McKay, Marcel Muelbaier, Carsten Schultz, Giovanna Bergamini
Click probes have enabled a thorough study of drug interactions in relevant disease models. Proper design of the probes, including the choice of the click moiety coupled to the drug, is crucial to ensure good performance and broad application. A new trans-cyclooctene derivative, amTCO, was synthesised using a phthalimide protecting group as a built-in photosensitiser for the cyclooctene isomerization. The 1-(aminomethyl)-trans-cyclooct-4-ene (amTCO) displays a primary amine group that facilitates conjugation with carboxylic acid or hydroxyl-containing compounds. It can help tuning the physical chemical properties of the resulting probes. An amTCO probe targeting indoleamine 2,3-dioxygenase (IDO1) was superior to a TCO variant. The new probe is an effective tool for visualizing IDO1 and measuring the binding affinities of small molecule inhibitors to IDO1 in cells.


Email Address of Submitting Author


European Molecular Biology Laboratory



ORCID For Submitting Author


Declaration of Conflict of Interest

C.E. worked under an agreement between EMBL, Cellzome GmbH and GlaxoSmithKline. A.R, D.T., L.E, B.M, M.M and G.B. are employees and/or shareholders of Cellzome GmbH and/or GlaxoSmithKline. C.S. is a consultant and a shareholder of SiChem GmbH. The remaining authors declare no competing financial interests.

Version Notes

IMPORTANT! I submitted this manuscript to ChemRxiv on 10th October 2020. I received a confirmation e-mail but the preprint was never made available online and disappeared from my submissions in my ChemRxiv account. I sent e-mails to the support team and the product manager but didn't get any answer. Therefore I am re-submitting. Please make sure this is not published twice. Thank you