Engineering galanin analogues that discriminate between GalR1 and GalR2 receptor subtypes and exhibit anticonvulsant activity following systemic delivery
| Autor: | Timothy H. Pruess, H. Steve White, Brad R. Green, Grzegorz Bulaj, Charles R. Robertson, Erika A. Scholl |
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| Rok vydání: | 2010 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class medicine.medical_treatment Molecular Sequence Data Neuropeptide Galanin receptor Galanin In Vitro Techniques Ligands Article Mice Radioligand Assay Structure-Activity Relationship Blood serum Internal medicine Drug Discovery medicine Animals Humans Amino Acid Sequence Receptor Chemistry digestive oral and skin physiology Biological activity Receptor Galanin Type 1 Rats Receptor Galanin Type 2 Endocrinology Anticonvulsant Molecular Medicine Anticonvulsants Calcium Oligopeptides |
| Zdroj: | Journal of medicinal chemistry. 53(4) |
| ISSN: | 1520-4804 |
| Popis: | Galanin modulates seizures in the brain through two galanin receptor subtypes, GalR1 and GalR2. To generate systemically-active galanin receptor ligands that discriminate between GalR1 and GalR2, the GalR1-preferring analogue, Gal-B2 (or NAX 5055), was rationally redesigned to yield GalR2-preferring analogues. Systematic truncations of the N-terminal backbone led to [N-Me, des-Sar]Gal-B2, containing N-methyl tryptophan: this analogue exhibited 18-fold preference in binding toward GalR2, maintained agonist activity, and exhibited potent anticonvulsant activity in mice following intraperitoneal administration. |
| Databáze: | OpenAIRE |
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