Discovery of novel small-molecule antagonists for GluK2
| Autor: | Derek Bowie, Nicolas Moitessier, Paolo Schiavini, G. Brent Dawe |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Protein Conformation Clinical Biochemistry Pharmaceutical Science Kainate receptor Ligands Biochemistry chemistry.chemical_compound Receptors Kainic Acid Catalytic Domain Drug Discovery Binding site Receptor Neurotransmitter Molecular Biology Molecular Structure Chemistry Organic Chemistry Glutamate receptor Rational design Small molecule 3. Good health Models Chemical Docking (molecular) Biophysics Molecular Medicine Software Central Nervous System Agents |
| Zdroj: | Bioorganicmedicinal chemistry letters. 25(11) |
| ISSN: | 1464-3405 |
| Popis: | KA receptors have shown to be potential therapeutic targets in CNS diseases such as schizophrenia, depression, neuropathic pain and epilepsy. Through the use of our docking tool Fitted, we investigated the relationship between ligand activity towards GluK2 and the conformational state induced at the receptor level. By focusing our rational design on the interaction between the ligand and a tyrosine residue in the binding site, we synthesized a series of molecules based on a glutamate scaffold, and carried out electrophysiological recordings. The observed ability of some of these molecules to inhibit receptor activation shows the potential of our design for the development of effective antagonists with a molecular size comparable to that of the endogenous neurotransmitter L-glutamate. |
| Databáze: | OpenAIRE |
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