研究组报道手性，两性离子有机硼络合物掩盖氨基酸衍生的KATs。这些分子表现出意想不到的氮-碳-硼连连性，并与固相肽合成和立体保护脱保护完全兼容。该课题组合成了C端KAT肽，并在微摩尔浓度下展示了KAT连接，用于聚合合成易于聚集的程序性死亡配体2 （PD-L2）免疫球蛋白V结构域。这项工作确立了有机硼化学作为一种低浓度的化学蛋白质合成策略，更适合处理大的、容易聚集的生物分子。
研究人员表示，化学蛋白质合成能够构建特定的蛋白质结构，但受限于毫摩尔反应浓度，限制了获得难溶蛋白质的途径。酰基三氟硼酸钾（KATs）通过快速和化学选择性的酰胺键形成提供了一种有希望的替代方案，但由于缺乏掩蔽策略，它们在蛋白质合成中的应用一直受到阻碍。
附：英文原文
Title: Zwitterionic organoboron complexes for overcoming the concentration barrier in chemical protein synthesis
Author: Philipp E. Schilling, Samuel Steiner, Jeffrey W. Bode
Issue&Volume: 2026-02-05
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.
DOI: aea7511
Source: https://www.science.org/doi/10.1126/science.aea7511