Ionic Liquid‐Mediated Approach for the Synthesis of Site‐Specific Thioether Conjugates

Bioconjugation methodologies have become a central part of therapeutic development. Conjugation of thiol-containing compounds is now simple with this ionic liquid-mediated reaction which is site-specific toward thiol and preserves the stereochemistry. Additionally, Cysteine-free peptides can be functionalized using the developed technique.
Abstract
Site-specific conjugation approaches are of great importance in drug discovery, notably for the synthesis of biochemical probes or molecular conjugates for targeted delivery. Herein, we report a mild ionic liquid (IL)-mediated thiolation technique that relies on the use of 1,3-ethyl-methyl imidazolium acetate, [C2mim][OAc] as a solvent and precursor to generate activated IL, as well as a solvent for the conjugation reaction. First, a focused library of active ILs was prepared for functionalizing/conjugating cysteine-containing small molecules and unprotected peptides. Interestingly, a bifunctional active IL could also be successfully employed as a linker for the conjugation of peptides lacking Cys. This study sets the ground for further investigation of the use of active ILs for modifying, labeling or conjugating larger and more complex therapeutic modalities such as proteins and antibodies.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Helal Abujubara, Jie Yang, A. Birsen Otyakmaz, Anaïs F. M. Noisier, Werngard Czechtizky, Malin Lemurell, Alesia A. Tietze
chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202203915