Document Report Card

Basic Information

ID: ALA2321677

Journal: Bioorg Med Chem

Title: Cyclic analogs of galanin and neuropeptide Y by hydrocarbon stapling.

Authors: Green BR, Klein BD, Lee HK, Smith MD, Steve White H, Bulaj G.

Abstract: Hydrocarbon stapling is an effective strategy to stabilize the helical conformation of bioactive peptides. Here we describe application of stapling to anticonvulsant neuropeptides, galanin (GAL) and neuropeptide Y (NPY), that are implicated in modulating seizures in the brain. Dicarba bridges were rationally introduced into minimized analogs of GAL and NPY resulting in increased α-helical content, in vitro metabolic stability and n-octanol/water partitioning coefficient (logD). The stapled analogs retained agonist activities towards their respective receptors and suppressed seizures in a mouse model of epilepsy.

CiteXplore: 23176753

DOI: 10.1016/j.bmc.2012.10.026