Kondrat’eva Ligation:
Diels–Alder-Based
Irreversible Reaction for Bioconjugation
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Abstract
Diversification of existing chemoselective
ligations is required
to efficiently access complex and well-defined biomolecular assemblies
with unique and valuable properties. The development and bioconjugation
applications of a novel Diels–Alder-based irreversible site-specific
ligation are reported. The strategy is based on a Kondrat’eva
cycloaddition between bioinert and readily functionalizable 5-alkoxyoxazoles
and maleimides that readily react together under mild and easily tunable
reaction conditions to afford a fully stable pyridine scaffold. The
potential of this novel bioconjugation is demonstrated through the
preparation of fluorescent conjugates of biomolecules and a novel
Förster resonance energy transfer (FRET)-based probe suitable
for the in vivo detection and imaging of urokinase-like plasminogen
activator (uPA), which is a key protease involved in cancer invasion
and metastasis