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Pentafulvene-Maleimide Cycloaddition for Bioorthogonal Ligation
Journal article   Peer reviewed

Pentafulvene-Maleimide Cycloaddition for Bioorthogonal Ligation

Kirsten Platts, Robert Michel, Elise Green, Todd Gillam, Maulik Ghetia, Neil O'Brien-Simpson, Wenyi Li, Christopher Blencowe, Anton Blencowe and Christopher B Rodell
Bioconjugate chemistry, v 32(8), pp 1845-1851
18 Aug 2021
PMID: 34254789

Abstract

Biomimetic Materials Biotin - chemistry Cyclopentanes - chemistry Hydrogen-Ion Concentration Maleimides - chemistry Molecular Structure
The applications of bioconjugation chemistry are rapidly expanding, and the addition of new strategies to the bioconjugation and ligation toolbox will further advance progress in this field. Herein, we present a detailed study of the Diels-Alder cycloaddition (DAC) reaction between pentafulvenes and maleimides in aqueous solutions and investigate the reaction as an emerging bioconjugation strategy. The DAC reactions were found to proceed efficiently, quantitatively yielding cycloadducts with reaction rates ranging up to ∼0.7 M s for a series of maleimides, including maleimide-derivatized peptides and proteins. The absence of cross-reactivity of the pentafulvene with a large panel of functional (bio)molecules and biological media further demonstrated the bioorthogonality of this approach. The utility of the DAC reaction for bioorthogonal bioconjugation applications was further demonstrated in the presence of biological media and proteins, as well as through protein derivatization and labeling, which was comparable to the widely employed sulfhydryl-maleimide coupling chemistry.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemical Research Methods
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry, Organic
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