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<p>Chirality is a fundamental characteristic of biological systems, resulting in marked differences in the in vivo activity and toxicity of enantiomeric drugs. Despite its significance, whether tissues/cells inherently possess the ability to recognize chiral drugs remains an open question. This study directly addresses this gap by developing Bio-Chiral Recognition Capillary Electrophoresis (BCRCE), a novel platform for probing drug-biomaterial interactions under near-physiological conditions. A key finding is that all tested rat tissues and cultured cells intrinsically exhibit distinct chiral recognition capabilities. The tissues and cells successfully differentiated enantiomers of drugs like thalidomide, lenalidomide, and pomalidomide, revealing both specific and non-specific interactions. Intriguingly, although omeprazole enantiomers were not distinguished, the racemate showed specific binding to certain tissues. Critically, BCRCE enabled the quantitative determination of binding kinetic parameters (<i>K</i>, <i>k</i><sub>a</sub>, <i>k</i><sub>d</sub>, and <i>k</i>’) for these interactions using non-linear chromatography theory. This work not only provides definitive evidence for intrinsic chiral recognition in biological systems but also establishes BCRCE as a powerful tool. BCRCE uniquely allows for the rapid screening, quantitative analysis, and kinetic profiling of chiral drugs in physiologically relevant contexts. It thereby holds great potential for guiding single-enantiomer drug selection, safety evaluation, and drug repurposing by elucidating tissue-specific chiral drug behaviors.</p>

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Novel Use of Tissues and Cells in Bio-Chiral Recognition Capillary Electrophoresis (BCRCE) for Chiral Recognition

  • 期刊论文

  • 发表日期：

    2026年7月31日

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  • Nurmuhammat Kehriman,
  • Wen Kuang,
  • Zuli Zhou,
  • Jilun Li,
  • Tao Huang,
  • Chunsu Liang,
  • Yi Liu,
  • Xiaomei Ling

摘要

Chirality is a fundamental characteristic of biological systems, resulting in marked differences in the in vivo activity and toxicity of enantiomeric drugs. Despite its significance, whether tissues/cells inherently possess the ability to recognize chiral drugs remains an open question. This study directly addresses this gap by developing Bio-Chiral Recognition Capillary Electrophoresis (BCRCE), a novel platform for probing drug-biomaterial interactions under near-physiological conditions. A key finding is that all tested rat tissues and cultured cells intrinsically exhibit distinct chiral recognition capabilities. The tissues and cells successfully differentiated enantiomers of drugs like thalidomide, lenalidomide, and pomalidomide, revealing both specific and non-specific interactions. Intriguingly, although omeprazole enantiomers were not distinguished, the racemate showed specific binding to certain tissues. Critically, BCRCE enabled the quantitative determination of binding kinetic parameters (K, ka, kd, and k’) for these interactions using non-linear chromatography theory. This work not only provides definitive evidence for intrinsic chiral recognition in biological systems but also establishes BCRCE as a powerful tool. BCRCE uniquely allows for the rapid screening, quantitative analysis, and kinetic profiling of chiral drugs in physiologically relevant contexts. It thereby holds great potential for guiding single-enantiomer drug selection, safety evaluation, and drug repurposing by elucidating tissue-specific chiral drug behaviors.