Philipp Schilling

All Publications

• Zwitterionic organoboron complexes for overcoming the concentration barrier in chemical protein synthesis SCIENCE Schilling, P. E., Steiner, S., Bode, J. W. 2026; 391 (6785): 598-603

  Abstract

  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. This work establishes organoboron chemistry as an enabling strategy for chemical protein synthesis at low concentrations far more suitable for handling large, aggregation-prone biomolecules.

  View details for DOI 10.1126/science.aea7511

  View details for Web of Science ID 001698264300012

  View details for PubMedID 41643010