Direct 11CN-labeling of unprotected peptides via palladium-mediated sequential cross-coupling reactions

Abstract

A practical procedure for [superscript 11]CN-labeling of unprotected peptides has been developed. The method was shown to be highly chemoselective for cysteine over other potentially nucleophilic residues, and the radiolabeled products were synthesized and purified in less than 15 min. Appropriate for biomedical applications, the method could be used on an extremely small scale (20 nmol) with a high radiochemical yield. The success of the protocol stems from the use of a Pd-reagent based on a dihaloarene, which enables direct “nucleophile-nucleophile” coupling of the peptide and [superscript 11]C cyanide by temporal separation of nucleophile addition.