Peptide Ligation via Suzuki-Miyaura Cross-Coupling Reaction

摘要

Functions of peptides can be improved or new ones be conferred by introducing molecules of different properties. Conjugation of peptides with cognate peptides, cell-permeable peptides, and PEG chains may enhance affinity to targets, cellular uptake, and metabolic stability, respectively. Furthermore, incorporation of chemical probes, such as fluorescent dyes and affinity tags, to peptides provides a useful tool for studying biological systems. Suzuki-Miyaura reaction, a palladium catalyzed cross-coupling reaction between a boronic acid and an organohalide or sulfonate, has a great potential inpeptide ligations due to advantages like bio-orthogonality and tolerance toward a broad range of functional groups [1,2]. However, the Suzuki-Miyaura reaction has been seldom used in peptide synthesis presumably because of relatively incompatible reaction conditions like a high reaction temperature in organic solvents [3-6]. In this study, we developed a method for chemoselective and bioorthogonal ligation of peptides via the Suzuki-Miyaura reaction. We also employed the method to conjugate various chemical probes to peptides.