ArticlebioRxiv : the preprint server for biology2026
SuFEx and macrocyclic chelation define orthogonal reactivity domains enabling isotopically versatile radiopharmaceuticals from a single peptide precursor.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The design of radiotheranostic agents has been constrained by a fundamental chemical incompatibility: existing strategies for fluorine-18 incorporation - nucleophilic substitution, silicon-fluoride exchange, aluminum fluoride chelation, and prosthetic conjugation - either require conditions incompatible with macrocyclic metal coordination, consume the chelator site needed for radiometal labeling, or introduce non-native structural appendages that alter pharmacokinetic behavior. Here we show that sulfur(VI) fluoride exchange (SuFEx) chemistry and macrocyclic metal coordination define non-overlapping reactivity domains co-embeddable within a single peptide precursor. An aryl fluorosulfate on tyrosine accepts
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