Peptidomimetic star polymers for targeting biological ion channels

Chen, Rong, Lu, Derong, Xie, Zili, Feng, Jing, Jia, Zhongfan, Ho, Junming, Coote, Michelle L., Wu, Yingliang, Monteiro, Michael J. and Chung, Shin-Ho (2016) Peptidomimetic star polymers for targeting biological ion channels. PLoS One, 11 3: e0152169-e0152169. doi:10.1371/journal.pone.0152169

Author Chen, Rong
Lu, Derong
Xie, Zili
Feng, Jing
Jia, Zhongfan
Ho, Junming
Coote, Michelle L.
Wu, Yingliang
Monteiro, Michael J.
Chung, Shin-Ho
Title Peptidomimetic star polymers for targeting biological ion channels
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-03-01
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.pone.0152169
Open Access Status DOI
Volume 11
Issue 3
Start page e0152169
End page e0152169
Total pages 10
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2017
Language eng
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Australian Institute for Bioengineering and Nanotechnology Publications
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