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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dahary, Dvir Soffer, Michal Ayalon Wool, Assaf Toporik, Amir Rotman, Galit Eshel, Dani Hecht, Iris Kliger, Yossef Rosenberg, Avi Levine, Zurit Shemesh, Ronen Cohen, Yossi Gofer, Eyal |
| Description | Author Affiliation: Shemesh R ( Compugen Limited, 72 Pinchas Rosen St., Tel Aviv 69512, Israel. ronens@compugen.co.il) |
| Abstract | G-protein-coupled receptors (GPCRs) represent an important group of targets for pharmaceutical therapeutics. The completion of the human genome revealed a large number of putative GPCRs. However, the identification of their natural ligands, and especially peptides, suffers from low discovery rates, thus impeding development of therapeutics based on these potential drug targets. We describe the discovery of novel GPCR ligands encrypted in the human proteome. Hundreds of potential peptide ligands were predicted by machine learning algorithms. In vitro screening of selected 33 peptides on a set of 152 GPCRs, including a group of designated orphan receptors, was conducted by intracellular calcium measurements and cAMP assays. The screening revealed eight novel peptides as potential agonists that specifically activated six different receptors in a dose-dependent manner. Most of the peptides showed distinct stimulatory patterns targeted at designated and orphan GPCRs. Further analysis demonstrated a significant in vivo effect for one of the peptides in a mouse inflammation model. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 50 |
| Volume Number | 283 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2008-12-12 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Receptors, G-Protein-Coupled Agonists Chemistry Algorithms Animals Computational Biology Cyclic AMP Dose-Response Relationship, Drug Drug Design Inflammation Ligands Mice Peptides Protein Binding Protein Engineering Proteomics Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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