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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\u2013derived 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.<\/jats:p>","DOI":"10.1126\/science.aea7511","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T19:00:52Z","timestamp":1770318052000},"page":"598-603","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Zwitterionic organoboron complexes for overcoming the concentration barrier in chemical protein synthesis"],"prefix":"10.1126","volume":"391","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-5367","authenticated-orcid":true,"given":"Philipp E.","family":"Schilling","sequence":"first","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry and Applied Bioscience, ETH Z\u00fcrich, Z\u00fcrich, 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