两性离子有机硼配合物克服化学蛋白质合成中的浓度障碍

Philipp E. Schilling†, Samuel Steiner, Jeffrey W. Bode* Chemical protein synthesis enables the construction of specific protein architectures but is limited to millimolar reaction concentrations, restricting access to poorly soluble proteins. Potassium acyltrifluoroboronates (KaTs) offer a promising alternative through fast and chemoselective amide bond formation, but their application to protein synthesis has been precluded by the lack of a masking strategy. We report chiral, zwitterionic organoboron complexes that mask amino acid–derived KaTs. These molecules exhibit unexpected nitrogen-carbon-boron connectivity and are fully compatible with solid-phase peptide synthesis and stereoretentive deprotection. We synthesized C-terminal KaT peptides and demonstrated KaT ligation at micromolar concentrations for the convergent synthesis of the aggregation-prone programmed death ligand 2 (PD-L2) immunoglobulin V domain. …