MrgX2-Targeting Ligand Screen for Antipseudoallergic Agents by Immobilized His-Tag-Fused Protein Technology

  • J Med Chem. 2025 Mar 13;68(5):5942-5953. doi: 10.1021/acs.jmedchem.5c00258.
Zhaomin Xia  1 ,  Qiumei Zhu  2 ,  Yi Shan  1 ,  Jiayu Lu  1 ,  Meidi An  1 ,  Xiaoxue Mo  1 ,  Siqi Wang  1 ,  Wen Yang  1 ,  Hua Qian  3 ,  Huaizhen He  1 ,  Cheng Wang  1
Affiliations
  • 1. School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 2. The 920th Hospital of Chinese People's Liberation Army Joint Logistics Support Force, Kunming, Yunnan 650100, China.
  • 3. Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
PMID: 40036663 DOI: 10.1021/acs.jmedchem.5c00258
Abstract

Mas-related G protein-coupled receptor X2 (MrgX2) plays a key role in pseudoallergy reactions; thus, it is of great significance to screen compounds with antipseudoallergy activity via MrgX2. Cell membrane chromatography (CMC) demonstrates great potential in drug screening, but it requires further optimization to improve its specificity and stability. In this study, a new CMC system incorporating His-tag-oriented immobilized proteins was constructed to screen MrgX2 antagonists. Single His-tag-fused MrgX2 was extracted intactly and covalently bond to divinyl sulfone-modified amino silica gel to obtain bioaffinity composites. The characterized composites were utilized to establish a MrgX2-His-tag@VS/CMC system to screen MrgX2 antagonists. Compound Z-3578 was screened from a G protein-coupled receptor compound library of 3010 compounds and revealed its efficient antipseudoallergy activity in vitro and in vivo via MrgX2. In conclusion, the new oriented-immobilized CMC system will provide an efficient analytical tool for screening active precursors.

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