Bioorganic & Medicinal Chemistry 2013-01-01

Cyclic analogs of galanin and neuropeptide Y by hydrocarbon stapling.

Brad R Green, Brian D Klein, Hee-Kyoung Lee, Misty D Smith, H Steve White, Grzegorz Bulaj

文献索引：Bioorg. Med. Chem. 21(1) , 303-10, (2013)

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摘要

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.Copyright © 2012 Elsevier Ltd. All rights reserved.