| Fluorescent stilbazolium dyes as probes of the norepinephrine transporter: structural insights into substrate binding. | |
| | |
MedLine Citation:
|
PMID: 23032519 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
We report the synthesis, binding kinetics, optical spectroscopy and predicted binding modes of a series of sterically demanding, fluorescent norepinephrine transporter (NET) ligands. A series of bulky stilbazolium dyes, including six newly synthesized compounds, were evaluated to determine the effect of extending the molecular probes' 'heads' or 'tails'. Taking advantage of the dyes' characteristic 'turn-on' emission, the kinetic binding parameters, k(on) and k(off) were determined revealing that extension of the molecules' tails is well tolerated while expansion of the head is not. Additionally, a 'headfirst' orientation appears to be preferred over a 'tail-first' binding pose. Further details of the possible binding modes were obtained from the emission spectra of the bound probes. A small range of interplanar twist angles, approximately 35° to 60°, is predicted to produce the observed emission. Docking experiments and molecular modelling support the kinetic and spectroscopic data providing structural insights into substrate binding. |
| | |
Authors:
|
James N Wilson; Adrienne S Brown; W Michael Babinchak; Clark D Ridge; Jamie D Walls |
Related Documents
:
|
19737939 - Regulation of interdomain interactions by calmodulin in inducible nitric-oxide synthase. 2452659 - Microtubule-associated protein, map2, is a calcium-binding protein. 12071969 - Interaction of bovine coagulation factor x and its glutamic-acid-containing fragments w... 7549869 - Characterization of the n-terminal half-saturated state of calbindin d9k: nmr studies o... 8415909 - Fluorescence lifetime and quenching studies of sarcoplasmic reticulum ca(2+)-adenosine-... 2096909 - Effects of calcium and calmodulin antagonists on calpain ii subunit conformations. 11755399 - Design and synthesis of a dimeric derivative of rk-682 with increased inhibitory activi... 7025879 - Dermatitis herpetiformis: immune complex detection with c1q and monoclonal rheumatoid f... 21438559 - Pulsating bead-based assay. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-10-3 |
Journal Detail:
|
Title: Organic & biomolecular chemistry Volume: - ISSN: 1477-0539 ISO Abbreviation: Org. Biomol. Chem. Publication Date: 2012 Oct |
Date Detail:
|
Created Date: 2012-10-3 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101154995 Medline TA: Org Biomol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Chemistry, University of Miami, 1301 Memorial Drive, Coral Gables, FL 33124, USA. jnwilson@miami.edu. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Antitumor effects and preliminary systemic toxicity of ANISpm in vivo and in vitro.
Next Document: Effect of Vitamin D3 Supplementation on Upper Respiratory Tract Infections in Healthy Adults: The VI...