Peptidomimetic star polymers for targeting biological ion channels

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

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5 Citations (Scopus)
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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.

Original languageEnglish
Article numbere0152169
Number of pages11
JournalPLoS One
Issue number3
Publication statusPublished - 23 Mar 2016
Externally publishedYes

Bibliographical note

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Peptidomimetic
  • Star polymers
  • Biological
  • ion channels
  • ionic currents


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