High impact information on 2-[6-[(5-dimethylaminonaphthalen-1-yl)sulfonylamino]hexanoyloxy]ethyl-trimethyl-azanium

• The compound with the most interesting properties (high affinity and selectivity for the acetylcholine binding site, as well as agonist activity and high photolabeling yield) is AC5, a structural analogue of the fluorescent agonist dansyl-C6-choline, which has been previously used to characterize the different states of the nicotinic receptor [1].
• To include any effects on the local potentials by the bound acceptor fluorophore crystal violet, its binding site was first localized within the pore by fluorescence energy transfer measurements from dansyl-C6-choline bound to the agonist sites and also by simulations of binding using Autodock [2].
• Examination of the binding kinetics of the fluorescent acetylcholine analog dansyl-C6-choline at ionic strengths from 12.5 to 400 mM revealed a twofold decrease in association rate [3].
• The KD for the low-affinity binding site was determined to be 1.1 microM from the increase in the amplitude of the fast decay with Dns-C6-Cho concentration with preincubation times that were sufficiently brief to minimize affinity state conversion [4].
• Agonist-induced desensitization was characterized from the time-dependent increase in fluorescence intensity that results from the binding of the fluorescent acetylcholine analog, Dns-C6-Cho, to the nAcChoR [5].

Biological context of 2-[6-[(5-dimethylaminonaphthalen-1-yl)sulfonylamino]hexanoyloxy]ethyl-trimethyl-azanium

• Stopped-flow fluorescence kinetics showed that dissociation of dansyl-C6-choline from the AChR in the desensitized conformation occurs 5-10-fold faster from the alpha gamma site than from the alpha delta site [6].

Anatomical context of 2-[6-[(5-dimethylaminonaphthalen-1-yl)sulfonylamino]hexanoyloxy]ethyl-trimethyl-azanium

• RESULTS: Mixing Dns-C6-Cho with nAcChoR-rich membranes results in an increase in fluorescence that is characterized by four rate processes [5].

References