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Updated: Jun 3, 2025

Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry
Published on: August 19, 2012
Water-Compatible Staudinger-Diels-Alder Ligation
Masaru Tanioka1, Shohei Kanayama1, Fumino Kitamura1
1Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Abstract:
The development of bioorthogonal reactions is expected to propel further advances in chemical biology. In this study, we demonstrate Staudinger-Diels-Alder (SDA) ligation as a candidate for a new bioorthogonal reaction. This reaction ligates two molecules via strong C-C bonds at room temperature. We found that the aryl substituent of azide-benzocyclobutene (azide-BCB) had a strong influence on the molecule's tolerance to water. In particular, Cl-substituted azide-BCBs generated the ligated product in high yield, even in the presence of water. Mechanistic investigations using DFT methods revealed that hydrophobic electron-withdrawing substituents suppressed the side reactions of SDA ligation.
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