Reversible Conjugation of Polypeptides and Proteins Utilizing a [3.3.1] Scaffold under Mild Conditions.

ABSTRACT

An investigation of reversible protein conjugation and deconjugation is presented. Despite numerous available protein conjugation methods, there has been limited documentation of achieving protein conjugation in a controlled and reversible manner. This report introduces a protocol that enables protein modification in a multicomponent fashion under aqueous buffer and mild conditions. A readily available mercaptobenzaldehyde derivative can modify the primary amine of peptides and proteins with a distinctive [3.3.1] scaffold. This modification can be reversed under mild conditions in a controlled fashion, restoring the original protein motif. The effectiveness of this approach has been demonstrated in the modification and quantifiable regeneration of insulin protein.