Engineering Galanin Analogues That Discriminate Between GalR1 and GalR2 Receptor Subtypes and Exhibit Anticonvulsant Activity Following Systemic Delivery

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2010 Feb 4

PMID 20121116

Citations 10

Authors

Charles R Robertson

Erika Adkins Scholl

Timothy H Pruess

Brad R Green

H Steve White

Grzegorz Bulaj

Affiliations

Soon will be listed here.

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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