Benzophenone photoprobes for chemical proteomics and drug target identification
Item
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Title
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Benzophenone photoprobes for chemical proteomics and drug target identification
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Identifier
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d_2009_2013:04fa118d61df:10921
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identifier
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11198
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Creator
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Mihai, Doina Mariana,
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Contributor
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Akira Kawamura
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Date
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2011
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Language
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English
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Publisher
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City University of New York.
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Subject
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Analytical chemistry | Pharmacy sciences
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Abstract
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Benzophenone photoprobes are widely used in photoaffinity-labeling studies, especially for the characterization of ligand-receptor interaction. Photolabeling studies using benzophenone, however, are by no means routine experiments. It is not uncommon that carefully designed photoligands fail to label target proteins. In order to get insights into the important factors that affect the photolabeling efficiency, we conducted a structure-activity relationship study (SAR) on adenine-benzophenone photoligands. The study suggested that conformational flexibility was the determining factor that controls the photolabeling efficiency by benzophenone photoprobes.;In theory, photoaffinity-labeling can also be used for target identification of small molecules. However, the complexity of proteins in biological samples, such as cell lysate, tissue homogenates and serum samples, limits the use of benzophenone photoprobes in drug target identification and chemical proteomics. By using so called "blocking strategy" we were able to systematically classify the list of proteins identified from photoaffinity-labeling studies using benzophenone. The findings of this study enabled us to refine the experimental protocol for drug target identification and chemical proteomics using benzophenone photoprobes.;During the affinity purification of phochemically biotinylated proteins, we discovered that monomeric avidin resin can selectively enrich heat shock proteins (Hsps) from complex proteomes. Although such serum Hsps or circulating Hsps, has been linked to various diseases, including cancer and cardiovascular diseases, their characterization have been hampered be the abundant proteins in serum such as albumin and immunoglobulings. The development of simple and reproducible method for Hsp enrichment opens a new opportunity to define the roles of circulating Hsps in various diseases.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Chemistry
