Biological and Medicinal Chemistry

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


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.

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


Thumbnail image of Echalier_amTCO_manuscript_ChemRxiv.pdf

Supplementary material

Thumbnail image of Echalier_amTCO_SI.pdf
Echalier amTCO SI