Characterization of the specific proteins to which HH-A, a drug that alleviates ischemic brain injury, binds in rat plasma
文献类型：期刊论文
| 作者 | Zhao, Jie3,4; Zheng, Yuandong4; Lei, Peng2; Zhang, Yuying1; Zhang, Pingping1; Liu, Ye1; Diao, Xingxing4 |
| 刊名 | DRUG METABOLISM AND DISPOSITION
 |
| 出版日期 | 2025-07-01 |
| 卷号 | 53期号:7页码:15 |
| 关键词 | Stroke Covalent binding HH-A Ischemic brain injury Proteomics |
| ISSN号 | 0090-9556 |
| DOI | 10.1016/j.dmd.2025.100102 |
| 通讯作者 | Diao, Xingxing(xxdiao@simm.ac.cn) |
| 英文摘要 | Stroke, a destructive and burdensome disease, continues to affect an increasing number of families. HH-A, also known as (S)-6-((3',5-diallyl-2,4'-dihydroxy-[1,1'-biphenyl]-3-yl)amino)-6-oxohexane-1,5-dia-minium chloride, has attracted attention for its ability to increase the oxygen-carrying capacity of hemoglobin and strongly alleviates ischemic brain injury in rat models of hypoxia. Owing to its low recovery rate after radioactive drug extraction, HH-A is thought to covalently bind to rat plasma proteins. In this study, intact protein, peptide, and amino acid analyses were performed on plasma samples via deconvolution of the intact protein, protein modification via proteomics, and protein mass spectrometry. HH-A was found to covalently bind to Lys413 of rat albumin. Molecular docking technology was used to simulate the binding mode of HH-A to rat albumin, the amino group of lysine is most likely to bind to the ortho-phenolic hydroxyl group judging from the reaction distance and the number of hydrogen bonds. This study demonstrated for the first time that honokiol and its derivatives (HH-A) covalently bind to rat plasma proteins and that the formation of new a,b-unsaturated aldehyde and ketone moieties in the drug is the key to these binding interactions. This experiment explains the binding mechanism of traditional Chinese medicine honokiol with plasma albumin at the molecular level, support the clinical research and development for HH-A. Significance statement: This study demonstrated that honokiol and its derivatives (a new drug HH-A, also known as (S)-6-((3',5-diallyl-2,4'-dihydroxy-[1,1'-biphenyl]-3-yl)amino)-6-oxohexane-1,5-diaminium chloride) covalently bind to rat plasma proteins via deconvolution of the intact protein, protein modification via proteomics, and protein mass spectrometry. This work supports the clinical research and development for HH-A. (c) 2025 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. |
| WOS关键词 | COVALENT BINDING ; PHENOLICS ; OXIDATION ; HONOKIOL ; ACID |
| 资助项目 | National Natural Science Foundation of China[82373938] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001514381100001 |
| 出版者 | ELSEVIER SCIENCE INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318474]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Diao, Xingxing |
| 作者单位 | 1.Beijing Honghui Meditech Co Ltd, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, Shanghai, Peoples R China 3.Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Ctr Drug Metab & Pharmacokinet Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Jie,Zheng, Yuandong,Lei, Peng,et al. Characterization of the specific proteins to which HH-A, a drug that alleviates ischemic brain injury, binds in rat plasma[J]. DRUG METABOLISM AND DISPOSITION,2025,53(7):15. |
| APA | Zhao, Jie.,Zheng, Yuandong.,Lei, Peng.,Zhang, Yuying.,Zhang, Pingping.,...&Diao, Xingxing.(2025).Characterization of the specific proteins to which HH-A, a drug that alleviates ischemic brain injury, binds in rat plasma.DRUG METABOLISM AND DISPOSITION,53(7),15. |
| MLA | Zhao, Jie,et al."Characterization of the specific proteins to which HH-A, a drug that alleviates ischemic brain injury, binds in rat plasma".DRUG METABOLISM AND DISPOSITION 53.7(2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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