PubMed 27007701

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.3

Title: Peptidomimetic Star Polymers for Targeting Biological Ion Channels.

Authors: Rong Chen, Derong Lu, Zili Xie, Jing Feng, Zhongfan Jia, Junming Ho, Michelle L Coote, Yingliang Wu, Michael J Monteiro, Shin-Ho Chung

Journal, date & volume: PLoS ONE, 2016 , 11, e0152169

PubMed link:

Four end-functionalized star polymers that could attenuate the flow of ionic currents across biological ion channels were first de novo designed computationally, then synthesized and tested experimentally on mammalian K+ channels. The 4-arm ethylene glycol conjugate star polymers with lysine or a tripeptide attached to the end of each arm were specifically designed to mimic the action of scorpion toxins on K+ channels. Molecular dynamics simulations showed that the lysine side chain of the polymers physically occludes the pore of Kv1.3, a target for immuno-suppression therapy. Two of the compounds tested were potent inhibitors of Kv1.3. The dissociation constants of these two compounds were computed to be 0.1 μM and 0.7 μM, respectively, within 3-fold to the values derived from subsequent experiments. These results demonstrate the power of computational methods in molecular design and the potential of star polymers as a new infinitely modifiable platform for ion channel drug discovery.