143965-99-5Relevant articles and documents
Chemical Targeting of Voltage Sensitive Dyes to Specific Cells and Molecules in the Brain
Fiala, Tomas,Wang, Jihang,Dunn, Matthew,?ebej, Peter,Choi, Se Joon,Nwadibia, Ekeoma C.,Fialova, Eva,Martinez, Diana M.,Cheetham, Claire E.,Fogle, Keri J.,Palladino, Michael J.,Freyberg, Zachary,Sulzer, David,Sames, Dalibor
, p. 9285 - 9301 (2020/06/04)
Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. The impact of these highly lipophilic sensors has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals. We address this key challenge by introducing a nongenetic molecular platform for cell- and molecule-specific targeting of synthetic VSDs in the brain. We employ a dextran polymer particle to overcome the inherent lipophilicity of VSDs by dynamic encapsulation and high-affinity ligands to target the construct to specific neuronal cells utilizing only native components of the neurotransmission machinery at physiological expression levels. Dichloropane, a monoamine transporter ligand, enables targeting of dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential changes in a similar manner to the parent dyes, as shown by whole-cell patch recording. We demonstrate the feasibility of optical voltage recording with our probes in brain tissue with one-photon and two-photon fluorescence microscopy and define the signal limits of optical voltage imaging with synthetic sensors under a low photon budget determined by the native expression levels of the target proteins. This work demonstrates the feasibility of a chemical targeting approach and expands the possibilities of cell-specific imaging and pharmacology.
Intermediates for the synthesis of radiolabelled tropanes
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Page 15, (2008/06/13)
The compounds of the present invention comprise a tropane compound or ligand that selectively binds to tropane recognition sites, e.g., neuron transporters such as that DAT. The tropane ligand is radiolabeled with a radioactive technetium or rhenium by a chelating ligand which is attached to the tropane ligand by a linker. Tropane compounds or ligands useful in the pratice of the present invention can generally be represented by formula II where R1 and R2 are defined as above and where R1 can also be substituted at the C4 position of the tropane ring: Any tropane compound of the general formula II is useful in the present invention so long as it binds to DAT. Useful tropane analogs have a 3α-group,i.e., are of the boat configuration. Intermediates for the synthesis of the radiolabeled tropanes are claimed.
COCAINE ANALOGUES AND THEIR USE AS COCAINE DRUG THERAPIES AND THERAPEUTIC AND IMAGING AGENTS FOR NEURODEGENERATIVE DISORDERS
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, (2008/06/13)
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