Peptide-based multiepitopic vaccine platforms via click reactions

Forner, Mar, 1980-; Defaus, Sira; Andreu Martínez, David

doi:http://dx.doi.org/10.1021/acs.joc.9b02798

Peptide-based multiepitopic vaccine platforms via click reactions

Citation

Forner M, Defaus S, Andreu D. Peptide-based multiepitopic vaccine platforms via click reactions. J Org Chem. 2020 Feb 7;85(3):1626-34. DOI: 10.1021/acs.joc.9b02798

Abstract

Multimeric antigen display and high overall valency are increasingly regarded as strategic goals for potent and broadly efficacious synthetic vaccines with potential market prospects. Herein, a modular and versatile approach to multifunctional peptide-based vaccine platforms at multimilligram scale in reasonable yields is reported. Preparation of chemoselectively modified peptide building blocks of medium-to-large size, conjugation of these subunits, and final assembly were achieved by a combination of Michael-type thiol-ene addition and copper(I)-mediated alkyne-azide cycloaddition. The size and structural complexity of the building blocks required exploration of a further level of orthogonality, namely furan/maleimide Diels-Alder chemistry. After process optimization, a finely tuned, stepwise click approach has emerged as a workable, on-demand strategy to create macromolecular therapeutic vaccine assemblies.