Novel and potent GPR35 agonists aid identification of residues important in ligand interaction

Mackenzie, A. E., Neetoo-Isseljee, Z., Southern, C., Jerman, J., McIver, E. G., Hudson, B. D. , Taylor, D. L. and Milligan, G. (2013) Novel and potent GPR35 agonists aid identification of residues important in ligand interaction. FASEB Journal, 27, 655.1.

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Abstract

The orphan G protein coupled receptor GPR35 has emerged as a therapeutic target in a number of disease states including metabolic disorder, cardiovascular disease, inflammation and nociception. Efforts to characterize this receptor, however, have been complicated by marked differences in the pharmacology of GPR35 species orthologs. We have identified novel agonist compounds with which to dissect the pharmacology and function of GPR35. Selected compounds were chosen to illustrate the differences in ligand structure activity relationship between human, mouse and rat orthologs of GPR35. Sequence alignment and receptor homology modeling techniques guided site directed mutagenesis, which highlighted a number of residues involved in GPR35 ligand interaction and revealed differences between rodent and human orthologs. These findings will benefit future drug development programs and efforts to generate therapeutically relevant GPR35-specific pharmacological compounds.

Item Type:Articles (Other)
Additional Information:Joint Annual Meeting of the ASPET/BPS at Experimental Biology
Meeting Abstract Supplement: 655.1
Status:Published
Refereed:No
Glasgow Author(s) Enlighten ID:Hudson, Dr Brian and Milligan, Professor Graeme and Mackenzie, Miss Amanda
Authors: Mackenzie, A. E., Neetoo-Isseljee, Z., Southern, C., Jerman, J., McIver, E. G., Hudson, B. D., Taylor, D. L., and Milligan, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:FASEB Journal
Publisher:FASEB
ISSN:0892-6638
ISSN (Online):1530-6860

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