Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor.
High-affinity blockers for an ion channel often have complex molecular structures that are synthetically challenging and/or laborious. Here we show that high-affinity blockers for the mouse nicotinic acetylcholine receptor (AChR) can be prepared from a structurally simple material, poly(ethylene gly...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4227698?pdf=render |
| _version_ | 1828917135844311040 |
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| author | Wan-Chen Lin Stuart Licht |
| author_facet | Wan-Chen Lin Stuart Licht |
| author_sort | Wan-Chen Lin |
| collection | DOAJ |
| description | High-affinity blockers for an ion channel often have complex molecular structures that are synthetically challenging and/or laborious. Here we show that high-affinity blockers for the mouse nicotinic acetylcholine receptor (AChR) can be prepared from a structurally simple material, poly(ethylene glycol) (PEG). The PEG-based blockers (PQ1-5), comprised of a flexible octa(ethylene glycol) scaffold and two terminal quaternary ammonium groups, exert low- to sub-micromolar affinities for the open AChR pore (measured via single-channel analysis of AChRs expressed in human embryonic kidney cells). PQ1-5 are comparable in pore-binding affinity to the strongest AChR open-channel blockers previously reported, which have complex molecular structures. These results suggest a general approach for designing potent open-channel blockers from a structurally flexible polymer. This design strategy involves simple synthetic procedures and does not require detailed information about the structure of an ion-channel pore. |
| first_indexed | 2024-12-13T20:45:42Z |
| format | Article |
| id | doaj.art-65e6738968bd456eb7d8fabe3966c292 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T20:45:42Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-65e6738968bd456eb7d8fabe3966c2922022-12-21T23:32:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11208810.1371/journal.pone.0112088Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor.Wan-Chen LinStuart LichtHigh-affinity blockers for an ion channel often have complex molecular structures that are synthetically challenging and/or laborious. Here we show that high-affinity blockers for the mouse nicotinic acetylcholine receptor (AChR) can be prepared from a structurally simple material, poly(ethylene glycol) (PEG). The PEG-based blockers (PQ1-5), comprised of a flexible octa(ethylene glycol) scaffold and two terminal quaternary ammonium groups, exert low- to sub-micromolar affinities for the open AChR pore (measured via single-channel analysis of AChRs expressed in human embryonic kidney cells). PQ1-5 are comparable in pore-binding affinity to the strongest AChR open-channel blockers previously reported, which have complex molecular structures. These results suggest a general approach for designing potent open-channel blockers from a structurally flexible polymer. This design strategy involves simple synthetic procedures and does not require detailed information about the structure of an ion-channel pore.http://europepmc.org/articles/PMC4227698?pdf=render |
| spellingShingle | Wan-Chen Lin Stuart Licht Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor. PLoS ONE |
| title | Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor. |
| title_full | Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor. |
| title_fullStr | Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor. |
| title_full_unstemmed | Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor. |
| title_short | Poly(ethylene glycol) as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor. |
| title_sort | poly ethylene glycol as a scaffold for high affinity open channel blockers of the mouse nicotinic acetylcholine receptor |
| url | http://europepmc.org/articles/PMC4227698?pdf=render |
| work_keys_str_mv | AT wanchenlin polyethyleneglycolasascaffoldforhighaffinityopenchannelblockersofthemousenicotinicacetylcholinereceptor AT stuartlicht polyethyleneglycolasascaffoldforhighaffinityopenchannelblockersofthemousenicotinicacetylcholinereceptor |