The Resource The effects of structural modifications on sigma receptor binding, by Rong Xu, (electronic resource)
The effects of structural modifications on sigma receptor binding, by Rong Xu, (electronic resource)
Resource Information
The item The effects of structural modifications on sigma receptor binding, by Rong Xu, (electronic resource) represents a specific, individual, material embodiment of a distinct intellectual or artistic creation found in University of Missouri-St. Louis Libraries.This item is available to borrow from all library branches.
Resource Information
The item The effects of structural modifications on sigma receptor binding, by Rong Xu, (electronic resource) represents a specific, individual, material embodiment of a distinct intellectual or artistic creation found in University of Missouri-St. Louis Libraries.
This item is available to borrow from all library branches.
- Summary
- The sigma receptor is a unique receptor family that has two subtypes: sigma1 and sigma2. Sigma1 receptors are involved in several physiological functions such as psychosis and depression. Sigma2 receptors are expressed in a variety of human tumors. Thus the selective sigma1 ligands have potential usage in central nervous system diseases, while sigma2 selective ligands can play an important role as biomarkers and therapeutic agents of tumor proliferation. Two well characterized compounds, SA4503 and conformationally flexible benzamide were chosen as our leads. Structural modifications were conducted in order to study the effect of structural elements on sigma binding properties; the possibility of new ligands as potential SPECT imaging agents was also explored. The result showed most of the SA4503 analogs had moderate affinity and no selectivity between sigma1 and sigma2 receptor subtype. All of these analogs had increased binding affinity for sigma2 subtype than their lead compound SA4503. The modifications made by replacing the left phenylpropyl group of SA4503 with an N-iodoallyl group yielded a sigma1 selective ligand (1h-7, E-IA-DM-PE-PIPZ) that had appropriate lipophilicity for penetrating the blood brain barrier in the CNS. The in vivo studies using radioiodinated 1h-7 showed that it had high specific binding to the sigma1 receptor in the mouse brain and thus it had great potential as SPECT agent for brain imaging. The modifications on the benzamide series of compounds by rigid dioxy rings showed similar trend in binding affinities as observed in the similar modification made on theSA4503 phenolic side chain, the most rigid methylenedioxy analog had the highest affinity and the least rigid propylenedioxy had the lowest affinity for sigma1 subtype. Sigma2 affinity was not affected significantly by the size of the dioxy ring. The modification of the strained tetrahydroisoquinoline ring with a freely rotating amine chain maintained the sigma1 affinity unchanged, while decreasing the sigma2 binding affinity dramatically. Thus a rigid tetrahydroisoquinoline is an important structural element for selective sigma2 binding in the benzamides series compounds
- Language
- eng
- Note
-
- The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file
- Title from title screen of research.pdf file (viewed on December 18, 2007)
- Vita
- Label
- The effects of structural modifications on sigma receptor binding
- Title
- The effects of structural modifications on sigma receptor binding
- Statement of responsibility
- by Rong Xu
- Language
- eng
- Summary
- The sigma receptor is a unique receptor family that has two subtypes: sigma1 and sigma2. Sigma1 receptors are involved in several physiological functions such as psychosis and depression. Sigma2 receptors are expressed in a variety of human tumors. Thus the selective sigma1 ligands have potential usage in central nervous system diseases, while sigma2 selective ligands can play an important role as biomarkers and therapeutic agents of tumor proliferation. Two well characterized compounds, SA4503 and conformationally flexible benzamide were chosen as our leads. Structural modifications were conducted in order to study the effect of structural elements on sigma binding properties; the possibility of new ligands as potential SPECT imaging agents was also explored. The result showed most of the SA4503 analogs had moderate affinity and no selectivity between sigma1 and sigma2 receptor subtype. All of these analogs had increased binding affinity for sigma2 subtype than their lead compound SA4503. The modifications made by replacing the left phenylpropyl group of SA4503 with an N-iodoallyl group yielded a sigma1 selective ligand (1h-7, E-IA-DM-PE-PIPZ) that had appropriate lipophilicity for penetrating the blood brain barrier in the CNS. The in vivo studies using radioiodinated 1h-7 showed that it had high specific binding to the sigma1 receptor in the mouse brain and thus it had great potential as SPECT agent for brain imaging. The modifications on the benzamide series of compounds by rigid dioxy rings showed similar trend in binding affinities as observed in the similar modification made on theSA4503 phenolic side chain, the most rigid methylenedioxy analog had the highest affinity and the least rigid propylenedioxy had the lowest affinity for sigma1 subtype. Sigma2 affinity was not affected significantly by the size of the dioxy ring. The modification of the strained tetrahydroisoquinoline ring with a freely rotating amine chain maintained the sigma1 affinity unchanged, while decreasing the sigma2 binding affinity dramatically. Thus a rigid tetrahydroisoquinoline is an important structural element for selective sigma2 binding in the benzamides series compounds
- Cataloging source
- MUU
- http://library.link/vocab/creatorDate
- 1977-
- http://library.link/vocab/creatorName
- Xu, Rong
- Degree
- Ph. D.
- Dissertation year
- 2007.
- Granting institution
- University of Missouri-Columbia
- Illustrations
- illustrations
- Index
- no index present
- Literary form
- non fiction
- Nature of contents
-
- dictionaries
- bibliography
- theses
- http://library.link/vocab/relatedWorkOrContributorName
- Lever, Susan Z., 1952-
- http://library.link/vocab/subjectName
-
- Sigma receptors
- Central nervous system
- Biochemical markers
- Analytical biochemistry
- Ligand binding (Biochemistry)
- Protein binding
- Target audience
- specialized
- Label
- The effects of structural modifications on sigma receptor binding, by Rong Xu, (electronic resource)
- Note
-
- The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file
- Title from title screen of research.pdf file (viewed on December 18, 2007)
- Vita
- Bibliography note
- Includes bibliographical references
- Carrier category
- online resource
- Carrier category code
-
- cr
- Carrier MARC source
- rdacarrier
- Color
- mixed
- Content category
- text
- Content type code
-
- txt
- Content type MARC source
- rdacontent
- Control code
- 184845644
- Dimensions
- unknown
- Form of item
- electronic
- Media category
- computer
- Media MARC source
- rdamedia
- Media type code
-
- c
- Specific material designation
- remote
- System control number
- (OCoLC)184845644
- System details
- Mode of access: World Wide Web
- Label
- The effects of structural modifications on sigma receptor binding, by Rong Xu, (electronic resource)
- Note
-
- The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file
- Title from title screen of research.pdf file (viewed on December 18, 2007)
- Vita
- Bibliography note
- Includes bibliographical references
- Carrier category
- online resource
- Carrier category code
-
- cr
- Carrier MARC source
- rdacarrier
- Color
- mixed
- Content category
- text
- Content type code
-
- txt
- Content type MARC source
- rdacontent
- Control code
- 184845644
- Dimensions
- unknown
- Form of item
- electronic
- Media category
- computer
- Media MARC source
- rdamedia
- Media type code
-
- c
- Specific material designation
- remote
- System control number
- (OCoLC)184845644
- System details
- Mode of access: World Wide Web
Library Locations
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St. Louis Mercantile LibraryBorrow it1 University Blvd, St. Louis, MO, 63121, US38.710138 -90.311107
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University ArchivesBorrow it703 Lewis Hall, Columbia, MO, 65211, US
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University of Missouri-St. Louis Libraries DepositoryBorrow it2908 Lemone Blvd, Columbia, MO, 65201, US38.919360 -92.291620
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University of Missouri-St. Louis Libraries DepositoryBorrow it2908 Lemone Blvd, Columbia, MO, 65201, US38.919360 -92.291620
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Ward E Barnes Education LibraryBorrow it8001 Natural Bridge Rd, St. Louis, MO, 63121, US38.707079 -90.311355
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<div class="citation" vocab="http://schema.org/"><i class="fa fa-external-link-square fa-fw"></i> Data from <span resource="http://link.umsl.edu/portal/The-effects-of-structural-modifications-on-sigma/1lwr-Eii-Vs/" typeof="Book http://bibfra.me/vocab/lite/Item"><span property="name http://bibfra.me/vocab/lite/label"><a href="http://link.umsl.edu/portal/The-effects-of-structural-modifications-on-sigma/1lwr-Eii-Vs/">The effects of structural modifications on sigma receptor binding, by Rong Xu, (electronic resource)</a></span> - <span property="potentialAction" typeOf="OrganizeAction"><span property="agent" typeof="LibrarySystem http://library.link/vocab/LibrarySystem" resource="http://link.umsl.edu/"><span property="name http://bibfra.me/vocab/lite/label"><a property="url" href="http://link.umsl.edu/">University of Missouri-St. Louis Libraries</a></span></span></span></span></div>
