Linked Life Data

18690702

Source:http://linkedlifedata.com/resource/pubmed/id/18690702

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2008-8-27
pubmed:abstractText
Blocking open ion channels provides a promising way to modulate synaptic transmission. Using the muscle-type acetylcholine receptor (AChR) as a test system, we seek to develop blockers that have blockade kinetics tunable via structural modifications. Here we investigate whether the blockade kinetics can be modulated by specifying the length of a poly(ethylene glycol) (PEG) spacer incorporated into the blocker. Single-channel electrophysiological experiments show that simple bis(trimethylammonium) compounds ( 1a- 3) both activate the AChR and block the open channel. The blockade kinetics are found to depend on spacer length: both the association and dissociation rate constants decrease with increasing spacer length. The decrease in the association rate constant can be quantitatively explained by the entropic cost of polymer confinement in the transmembrane lumen, while the decrease in the dissociation rate constant is consistent with weak, additive noncovalent interactions between the channel and the spacer. These results provide useful insights into the future design of kinetically tunable open-channel blockers for the AChR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9163-73
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Polymer-based open-channel blockers for the acetylcholine receptor: the effect of spacer length on blockade kinetics.
pubmed:affiliation
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't