An antibody is a protein that is produced in response to and counteracting a specific antigen and when linked with a drug it creates an antibody-drug conjugate (ADC). The major impediment of the formation of the linkage between an antibody and cytotoxin is the difficulty of performing selective chemical reactions in aqueous solution. In this work, ionic liquids, which are ionic organic salts with a liquid state of &lt;100<sup>○</sup>C, have been employed as an alternative reaction medium. This study proved that ionic liquids serve as a novel reaction solvent for bioconjugation while keeping the biomolecules’ functionality. The bioconjugation discovery program using ionic liquids led to the discovery of a triphenylphosphine-mediated amine-azide coupling reaction that creates a stable tetrazene linkage. This reaction was screened on a variety of amines-containing molecules, to determine the selectivity toward alkylamine groups. The bioconjugation reaction was also screened on antibiotics and hormones, as well as more, which can be used for larger application. This work was translated into an antibody modification creating an ADC, which did not display any noticeable loss of its native functionality after the treatment with ionic liquid-based reaction conditions. In addition to the reaction screening, effective purification method of the labeled biomolecules after the ionic liquid reactions have been optimized.

Reactivity survey and purification method development for ionic liquid based bioconjugation

ACS Spring 2022

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