Demonstrates rapid assembly of multicyclic peptides in aqueous conditions, suggesting new methods for peptide synthesis.
Sandwich-SuFEx (sulfur(VI) fluoride exchange) cyclization is introduced as a rapid, aqueous cross-linking reaction complementary to CuAAC and thioether formation. Di- or triarmed aryl sulfonyl fluorides selectively capture peptide phenols to afford terphenyl-bridged macrocycles spanning 5- to 12-mers, tolerating diverse side chains and linker designs. One-pot reactions combining sandwich-SuFEx with thioether formation assemble bi-, tri-, and tetracyclic peptides with tunable topologies in <1 h, expanding the toolbox for aqueous multicycle assembly.
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Mi et al. (2026) studied this question.
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