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Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2020

Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction

Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction.

Résumé

The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs' functionalization to allow high TCO/tetrazine cycloaddition.
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Dates et versions

hal-02909484 , version 1 (18-07-2022)

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Paternité - Pas d'utilisation commerciale

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Jean-Baptiste Béquignat, Nancy Ty, Aurélie Rondon, Ludivine Taiariol, Françoise Degoul, et al.. Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction. European Journal of Medicinal Chemistry, 2020, 203, pp.112574. ⟨10.1016/j.ejmech.2020.112574⟩. ⟨hal-02909484⟩
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