Forner, Mar, 1980-Defaus, SiraAndreu Martínez, David2025-10-282025-10-282020Forner 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.9b027980022-3263http://hdl.handle.net/10230/71682Multimeric 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.application/pdfengThis document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of organic chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.joc.9b02798.info:eu-repo/semantics/article2025-10-28http://dx.doi.org/10.1021/acs.joc.9b02798Chemical reactionsHigh-performance liquid chromatographyMonomersPeptides and proteinsPhosphatesinfo:eu-repo/semantics/openAccess