Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

Yonghua Lei; Tianhan Hu; Xingsen Wu; Yue Wu; Qichao Bao; Lianshan Zhang; Hua Xia; Haopeng Sun; Qidong You; Xiaojin Zhang

doi:10.1021/acsmedchemlett.5b00394

Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

Yonghua Lei
, Tianhan Hu
, Xingsen Wu
, Yue Wu
, Qichao Bao
, Lianshan Zhang
, Hua Xia
, Haopeng Sun
, Qidong You
, Xiaojin Zhang

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Prolyl hydroxylase domain 2 (PHD2) enzyme, a Fe^II and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.

Original language	English (US)
Pages (from-to)	1236-1240
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	6
Issue number	12
DOIs	https://doi.org/10.1021/acsmedchemlett.5b00394
State	Published - Dec 10 2015
Externally published	Yes

Keywords

FITC-labeled probe
PHD2
affinity-based
fluorescence polarization assay

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1021/acsmedchemlett.5b00394

Cite this

@article{4c397cff46f8454a8c68ebb4037426e3,

title = "Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors",

abstract = "Prolyl hydroxylase domain 2 (PHD2) enzyme, a FeII and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.",

keywords = "FITC-labeled probe, PHD2, affinity-based, fluorescence polarization assay",

author = "Yonghua Lei and Tianhan Hu and Xingsen Wu and Yue Wu and Qichao Bao and Lianshan Zhang and Hua Xia and Haopeng Sun and Qidong You and Xiaojin Zhang",

note = "Publisher Copyright: {\textcopyright} 2015 American Chemical Society.",

year = "2015",

month = dec,

day = "10",

doi = "10.1021/acsmedchemlett.5b00394",

language = "English (US)",

volume = "6",

pages = "1236--1240",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

number = "12",

}

TY - JOUR

T1 - Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

AU - Lei, Yonghua

AU - Hu, Tianhan

AU - Wu, Xingsen

AU - Wu, Yue

AU - Bao, Qichao

AU - Zhang, Lianshan

AU - Xia, Hua

AU - Sun, Haopeng

AU - You, Qidong

AU - Zhang, Xiaojin

PY - 2015/12/10

Y1 - 2015/12/10

N2 - Prolyl hydroxylase domain 2 (PHD2) enzyme, a FeII and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.

AB - Prolyl hydroxylase domain 2 (PHD2) enzyme, a FeII and 2-oxoglutarate (2-OG) dependent oxygenase, mediates key physiological responses to hypoxia by modulating the levels of hypoxia inducible factor 1-α (HIF1α). PHD2 has been shown to have the therapeutic potentials for conditions including anemia and ischemic disease. Currently, many activity-based assays have been developed for identifying PHD2 inhibitors. Here we report an affinity-based fluorescence polarization method using FITC-labeled HIF1α (556-574) peptide as a probe for quantitative and site-specific screening of small molecule PHD2 inhibitors.

KW - FITC-labeled probe

KW - PHD2

KW - affinity-based

KW - fluorescence polarization assay

UR - https://www.scopus.com/pages/publications/84949782397

UR - https://www.scopus.com/pages/publications/84949782397#tab=citedBy

U2 - 10.1021/acsmedchemlett.5b00394

DO - 10.1021/acsmedchemlett.5b00394

M3 - Article

AN - SCOPUS:84949782397

SN - 1948-5875

VL - 6

SP - 1236

EP - 1240

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 12

ER -

Affinity-Based Fluorescence Polarization Assay for High-Throughput Screening of Prolyl Hydroxylase 2 Inhibitors

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this