Next Article in Journal
Facile Preparation of the Tosylhydrazone Derivatives of a Series of Racemic trans-3,4-Substituted Cyclopentanones
Previous Article in Journal
Cleavage of Oligonucleotides Containing a P3’→N5’ Phosphoramidate Linkage Mediated by Single-Stranded Oligonucleotide Templates
Article Menu

Article Versions

Export Article

Open AccessArticle
Molecules 2011, 16(12), 10709-10721; doi:10.3390/molecules161210709

Fluorescence Resonance Energy Transfer Assay for High-Throughput Screening of ADAMTS1 Inhibitors

1
Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China
2
Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA
*
Author to whom correspondence should be addressed.
Received: 4 November 2011 / Revised: 6 December 2011 / Accepted: 13 December 2011 / Published: 20 December 2011
Download PDF [417 KB, uploaded 18 June 2014]

Abstract

A disintegrin and metalloprotease with thrombospondin type I motifs-1 (ADAMTS1) plays a crucial role in inflammatory joint diseases and its inhibitors are potential candidates for anti-arthritis drugs. For the purposes of drug discovery, we reported the development and validation of fluorescence resonance energy transfer (FRET) assay for high-throughput screening (HTS) of the ADAMTS1 inhibitors. A FRET substrate was designed for a quantitative assay of ADAMTS1 activity and enzyme kinetics studies. The assay was developed into a 50-µL, 384-well assay format for high throughput screening of ADAMTS1 inhibitors with an overall Z’ factor of 0.89. ADAMTS1 inhibitors were screened against a diverse library of 40,960 total compounds with the established HTS system. Four structurally related hits, naturally occurring compounds, kuwanon P, kuwanon X, albafuran C and mulberrofuran J, extracted from the Chinese herb Morus alba L., were identified for further investigation. The results suggest that this FRET assay is an excellent tool, not only for measurement of ADAMTS1 activity but also for discovery of novel ADAMTS1 inhibitors with HTS.
Keywords: ADAMTS1; inhibitor; high-throughput screening; fluorescence resonance energy transfer; drug discovery ADAMTS1; inhibitor; high-throughput screening; fluorescence resonance energy transfer; drug discovery
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Peng, J.; Gong, L.; Si, K.; Bai, X.; Du, G. Fluorescence Resonance Energy Transfer Assay for High-Throughput Screening of ADAMTS1 Inhibitors. Molecules 2011, 16, 10709-10721.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top