Screening of prolyl hydroxylase 2 inhibitors based on quantitative strategy of peptides | |
Department | 中科院西北特色植物资源化学重点实验室/甘肃省天然药物重点实验室 |
Ying Zhang1,2; Stanislas Nsanzamahoro1,2; Cheng-Bo Wang1; Wei-Feng Wang1; Jun-Li Yang1 | |
The second department | 药物化学与新药分子研究团队 |
2022 | |
Source Publication | Journal of Chromatography A |
Issue | 1679Pages:463411 |
Abstract | Prolyl hydroxylase 2 (PHD2) is a key oxygen receptor regulating oxygen homeostasis in human body, and it is one of the important targets for drug research and development of hypoxia related diseases. In PHD2 enzymatic reaction, the structure of substrate (HIF-1 α556–574) and product (hydroxylated HIF-1 α) peptide only differ from one oxygen atom (MW > 20 0 0), which makes it a great challenge to separate them accu- rately and efficiently. In this work, the direct separation and detection of HIF-1 αand hydroxylated HIF- 1 αhas been firstly reported based on micellar electrokinetic chromatography (MEKC). Under optimized conditions, the intraday RSD of peak area and apparent electrophoretic mobility of hydroxylated HIF-1 αwere 1.87% and 0.81% respectively, and the interday RSD were 2.01% and 1.03% respectively. The LOD and LOQ of the MEKC method were 10 μM and 50 μM respectively, and the recoveries was 98.42–105.38%. Subsequently, the feasibility and accuracy of MEKC method to screen PHD2 inhibitors were confirmed by using roxadustat, and the IC 50 (10.36 μM) and inhibitor type (competitive) were consistent with lit- erature. Finally, the method was used to screen the PHD2 inhibitory activity of five traditional Chinese medicines (TCMs). The present work not only overcomes the difficulties of direct quantitative detection of hydroxylated HIF-1 α, but also provides technical support for exploring and discovering new drug leads for hypoxia-related diseases from complex matrix such as TCMs. |
Keyword | Prolyl hydroxylase 2 Traditional Chinese medicine Hypoxia related diseases Micellar electrokinetic chromatography |
DOI | 10.1016/j.chroma.2022.463411 |
If | 4.601 |
Language | 英语 |
compositor | 第一作者单位 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.licp.cn/handle/362003/29275 |
Collection | 中科院西北特色植物资源化学重点实验室/甘肃省天然药物重点实验室 |
Corresponding Author | Wei-Feng Wang; Jun-Li Yang |
Affiliation | 1.Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS) 2.University of Chinese Academy of Sciences |
Recommended Citation GB/T 7714 | Ying Zhang,Stanislas Nsanzamahoro,Cheng-Bo Wang,et al. Screening of prolyl hydroxylase 2 inhibitors based on quantitative strategy of peptides[J]. Journal of Chromatography A,2022(1679):463411. |
APA | Ying Zhang,Stanislas Nsanzamahoro,Cheng-Bo Wang,Wei-Feng Wang,&Jun-Li Yang.(2022).Screening of prolyl hydroxylase 2 inhibitors based on quantitative strategy of peptides.Journal of Chromatography A(1679),463411. |
MLA | Ying Zhang,et al."Screening of prolyl hydroxylase 2 inhibitors based on quantitative strategy of peptides".Journal of Chromatography A .1679(2022):463411. |
Files in This Item: | ||||||
File Name/Size | DocType | Version | Access | License | ||
2022 JCA-Screening o(1364KB) | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | View Application Full Text |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment