Abstract |
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-methyltryptophan. This analogue exhibited 18-fold preference in binding toward GalR2, maintained agonist activity, and exhibited potent anticonvulsant activity in mice following intraperitoneal administration.
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Authors | Charles R Robertson, Erika Adkins Scholl, Timothy H Pruess, Brad R Green, H Steve White, Grzegorz Bulaj |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 53
Issue 4
Pg. 1871-5
(Feb 25 2010)
ISSN: 1520-4804 [Electronic] United States |
PMID | 20121116
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticonvulsants
- Ligands
- Oligopeptides
- Receptor, Galanin, Type 1
- Receptor, Galanin, Type 2
- Galanin
- Calcium
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Topics |
- Amino Acid Sequence
- Animals
- Anticonvulsants
(chemical synthesis, chemistry, pharmacology)
- Calcium
(metabolism)
- Galanin
(analogs & derivatives, chemical synthesis, chemistry, pharmacology)
- Humans
- In Vitro Techniques
- Ligands
- Mice
- Molecular Sequence Data
- Oligopeptides
(chemical synthesis, chemistry, pharmacology)
- Radioligand Assay
- Rats
- Receptor, Galanin, Type 1
(agonists, metabolism)
- Receptor, Galanin, Type 2
(agonists, metabolism)
- Structure-Activity Relationship
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