Peptide Ligation via the Suzuki-Miyaura Cross-Coupling Reaction.

Chemoselective ligation of two 28-mer peptides has been accomplished using the Suzuki-Miyaura cross-coupling reaction at or near physiological temperature in an aqueous solution containing sodium dodecyl sulfate in 83% yield. The effects of Pd source, solvent, base, and temperature were investigated, and the optimized reaction conditions were studied for compatibility with naturally present and artificially introduced functional groups in peptides including S-protected thiol and azide. The peptide conjugations were carried out in high yield (90%) with their functional groups intact. This method also allowed for facile introduction of an affinity tag or fluorescent probe into 20-mer peptides in >80% yield. These results suggest that the Suzuki-Miyaura cross-coupling is useful for multiple conjugations of peptides in conjunction with conventional conjugation reactions performed in sequence.