タンパク質抱合体におけるパセリーニ多成分生体抱合およびイソシアノプロテインを用いた一分子多価多様性の創出

Ana R Humpierre^1,2, Yanira Méndez^1,3, Ahyoung Kim¹

¹Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, Halle/Saale, Germany.

|January 21, 2026

Abstract:

The ability to conjugate multiple molecules to a protein is of great interest for pharmaceutical and vaccine development, especially if this can be achieved in a one-pot procedure. Multicomponent reactions are powerful procedures that allow the assembly of complex constructs incorporating at least three molecular fragments, but many of them use amino and carboxylic groups that are too abundant in proteins. Herein, we introduce the use of the Passerini 3-component reaction with isocyanoproteins for the assembly of multivalent protein (glyco)conjugates. Proteins were tagged with isocyanide handles and next derivatized to investigate the efficacy and limitations of the Passerini bioconjugation. The multicomponent conjugation enabled the simultaneous functionalization of proteins with two biologically relevant molecules such as carbohydrate antigens, lipids, and polymers. The efficient display of various antigens in a unimolecular multivalent construct is a notable result that paves the way towards new applications in preventive vaccines and therapeutics.

キーワード:

多価タンパク質抱合体パセリーニ反応生体抱合ワクチン開発治療薬開発一分子多価性イソシアノプロテイン

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