Engineering galanin analogues that discriminate between GalR1 and GalR2 receptor subtypes and exhibit anticonvulsant activity following systemic delivery.

@article{Robertson2010EngineeringGA,
  title={Engineering galanin analogues that discriminate between GalR1 and GalR2 receptor subtypes and exhibit anticonvulsant activity following systemic delivery.},
  author={Charles R Robertson and Erika Adkins Scholl and Timothy H. Pruess and Brad Green and Henry S White and Grzegorz Bulaj},
  journal={Journal of medicinal chemistry},
  year={2010},
  volume={53 4},
  pages={1871-5}
}
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… CONTINUE READING