Journal article
A screening library for peptide activated G-protein coupled receptors. 1. The test set
Journal of medicinal chemistry, v 47(27), pp 6864-6874
30 Dec 2004
PMID: 15615535
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
One subset of the G-protein coupled receptor (GPCR) superfamily is that which is activated by a peptide carrying an obligatory positively charged residue (GPCR-PA(+)). This subclass is exemplified by receptors for melanocortins, GnRH, galanin, MCH, orexin, and some chemokine receptors variously involved in eating disorders, reproductive disorders, pain, narcolepsy, obesity, and inflammation. Using the methods described in this study, a region of chemical property space enriched in GPCR ligands was identified. This information was used to design and synthesize a "test" library of 2025 single, pure compounds to sample portions of this property space associated with GPCR-PA(+) ligands. The library was evaluated by high-throughput screening against three different receptors, rMCH, hMC4, and hGnRH, and found to be highly enriched in active ligands (4.5-61-fold) compared to a control set of 2024 randomly selected compounds. In addition, the analysis suggested that about 7000 compounds will be necessary to complete the sampling of this GPCR-PA(+) ligand-rich region and to better define its borders.
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Details
- Title
- A screening library for peptide activated G-protein coupled receptors. 1. The test set
- Creators
- Karine Lavrador - Neurocrine Biosciences (United States)Brian Murphy - Neurocrine Biosciences (United States)John Saunders - Neurocrine Biosciences (United States)Scott Struthers - Neurocrine Biosciences (United States)Xiaochuan Wang - Neurocrine Biosciences (United States)John Williams - Neurocrine Biosciences (United States)
- Publication Details
- Journal of medicinal chemistry, v 47(27), pp 6864-6874
- Publisher
- American Chemical Society (ACS)
- Grant note
- 5R44 GM61491-03 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000225952400025
- Scopus ID
- 2-s2.0-11144237578
- Other Identifier
- 991021902523804721
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- Web of Science research areas
- Chemistry, Medicinal