Double Conjugation Using Mercapto-Acryloyl and Alkyne-Azide Reactions for the Synthesis of Branched Multiantigenic Vaccine Candidates.

Chemical conjugation of peptide epitopes and lipids into a single branched lipopeptide is a promising strategy for the generation of multiantigenic vaccines. We developed a double conjugation strategy that utilizes a mercapto-acryloyl Michael addition reaction between two unprotected peptides, followed by a copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) click reaction. The technique proved capable of producing branched multiantigenic vaccine candidates with an overall yield of 78%.