Source:http://linkedlifedata.com/resource/pubmed/id/15725002
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2005-2-23
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pubmed:abstractText |
Cocaine is a highly addictive drug, and despite intensive efforts, effective therapies for cocaine craving and addiction remain elusive. In recent years, we and others have reported advances in anti-cocaine immunopharmacotherapy based on specific antibodies capable of sequestering the drug before it reaches the brain. In an effort to obtain high affinity therapeutic anti-cocaine antibodies, either whole IgGs or other antibody constructs, fluorescence spectroscopic techniques could provide a means of assisting selection and engineering strategies. We report the synthesis of a series of cocaine-fluorophore conjugates (GNC-F1, GNC-F2, GNC-I) and the functional evaluation of these compounds against single-chain Fv antibodies obtained via crystallographic analysis/engineering and against commercially available anti-cocaine monoclonal antibodies with a wide range of cocaine-binding affinities. From these studies, we determined that the GNC-F2 fluorophore reproduced affinity constants obtained using [(3)H]-labeled cocaine. We anticipate that the readily synthesized and nonradioactive GNC-F2 will find use both as a tool for bioimaging and in the high-throughput selection and engineering of potential therapeutic antibodies against cocaine.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Library
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0002-7863
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
127
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2477-84
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15725002-Animals,
pubmed-meshheading:15725002-Antibodies, Monoclonal,
pubmed-meshheading:15725002-Base Sequence,
pubmed-meshheading:15725002-Cocaine,
pubmed-meshheading:15725002-Fluorescent Dyes,
pubmed-meshheading:15725002-Humans,
pubmed-meshheading:15725002-Immunoconjugates,
pubmed-meshheading:15725002-Immunoglobulin Fragments,
pubmed-meshheading:15725002-Immunoglobulin G,
pubmed-meshheading:15725002-Kinetics,
pubmed-meshheading:15725002-Mice,
pubmed-meshheading:15725002-Models, Molecular,
pubmed-meshheading:15725002-Molecular Sequence Data,
pubmed-meshheading:15725002-Peptide Library,
pubmed-meshheading:15725002-Protein Engineering,
pubmed-meshheading:15725002-Spectrometry, Fluorescence
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pubmed:year |
2005
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pubmed:articleTitle |
Fluorescent cocaine probes: a tool for the selection and engineering of therapeutic antibodies.
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pubmed:affiliation |
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, BCC-582, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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