1
40
2
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Text
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<a href="http://doi.org/10.1016/j.bmcl.2009.12.088" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2009.12.088</a>
Pages
819–823
Issue
3
Volume
20
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Structure-based design of a thiazolidinedione which targets the mitochondrial protein mitoNEET.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-02
Subject
The topic of the resource
*Drug Design; Animals; Binding Sites/drug effects/physiology; Dose-Response Relationship; Drug; Drug Delivery Systems/*methods; Liver/drug effects/metabolism; Mitochondria; Mitochondrial Proteins/*metabolism; Protein Structure; Rats; Secondary; Structure-Activity Relationship; Thiazolidinediones/administration & dosage/*chemical synthesis/*metabolism
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Funk Max O; Barnes Kendra F; Carroll Richard T
Description
An account of the resource
Several PPAR-gamma agonists containing a thiazolidinedione moiety (referred to as glitazones) have been proposed to be neuroprotective and appear to alter mitochondrial function. Recently, a search for mitochondrial proteins that bind pioglitazone identified a novel protein, mitoNEET, which was later shown to regulate the oxidative capacity of the mitochondria. This identified an alternative target for the glitazones suggesting a possible new drug target for the treatment of neurodegenerative diseases. Molecular docking studies employing the reported crystal structure revealed five possible binding pockets on mitoNEET. We focused on two sites based on their physical characteristics. Using binding information gained from the analysis of two glitazones docked in these pockets, we designed and synthesized a ligand (NL-1) that would preferentially bind to site 1. Based on [(3)H]-binding data of the glitazones and comparisons to computer generated K(i)s, we were able to predict that site 1 was likely the target of the glitazones. NL-1 uncoupled isolated mitochondrial complex I respiration with an IC(50) of 2.4 microM and inhibited state III respiration up to 45%. To investigate the ability of NL-1 to block rotenone initiated free radicals from complex I, we found it was able to protect the human neuronal cell line SH-SY5Y against rotenone induced cell death. These data demonstrate that mitoNEET is a viable target for the design and synthesis of novel therapeutic agents aimed at altering mitochondrial function.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2009.12.088" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2009.12.088</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Drug Design
2010
Animals
Barnes Kendra F
Binding Sites/drug effects/physiology
Bioorganic & medicinal chemistry letters
Carroll Richard T
Dose-Response Relationship
Drug
Drug Delivery Systems/*methods
Funk Max O
Geldenhuys Werner J
Liver/drug effects/metabolism
Mitochondria
Mitochondrial Proteins/*metabolism
Protein Structure
Rats
Secondary
Structure-Activity Relationship
Thiazolidinediones/administration & dosage/*chemical synthesis/*metabolism
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.bmcl.2016.09.009" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2016.09.009</a>
Pages
5350–5353
Issue
21
Volume
26
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Identification of small molecules that bind to the mitochondrial protein mitoNEET.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-11
Subject
The topic of the resource
*Bioenergetics; *Glitazones; *Mitochondria; *Small Molecule Libraries; *Type II diabetes; Hypoglycemic Agents/chemistry/metabolism; Ligands; Mitochondrial Proteins/*metabolism; Protein Binding; Thiazolidinediones/chemistry/metabolism
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Yonutas Heather M; Morris Daniel L; Sullivan Patrick G; Darvesh Altaf S; Leeper Thomas C
Description
An account of the resource
MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements. We found that the thiazolidinedione (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for binding to mitoNEET. These results will aid in the development of novel compounds that can be used to treat mitochondrial dysfunction seen in several diseases.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2016.09.009" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2016.09.009</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Bioenergetics
*Glitazones
*Mitochondria
*Small Molecule Libraries
*Type II diabetes
2016
Bioorganic & medicinal chemistry letters
Darvesh Altaf S
Department of Pharmaceutical Sciences
Geldenhuys Werner J
Hypoglycemic Agents/chemistry/metabolism
Leeper Thomas C
Ligands
Mitochondrial Proteins/*metabolism
Morris Daniel L
NEOMED College of Pharmacy
Protein Binding
Sullivan Patrick G
Thiazolidinediones/chemistry/metabolism
Yonutas Heather M