Source:http://linkedlifedata.com/resource/pubmed/id/17502149
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
2007-6-6
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pubmed:abstractText |
Four novel water-soluble peptide-paclitaxel conjugates were designed and synthesized as prostate-specific antigen (PSA)-activated prodrugs for prostate cancer therapy. These prodrugs were composed of a peptide, HSSKLQ or SSKYQ, each of which is selectively cleavable by PSA; a self-immolative linker, either para-aminobenzyl alcohol (PABS) or ethylene diamine (EDA); and the parent drug, paclitaxel. Introduction of a PABA or EDA linker between the peptide and paclitaxel in prodrugs 2-5 resulted in products with an increased rate of hydrolysis by PSA. The stability of prodrugs 2 and 3, with the PABA linker, was poor in the serum-containing medium because of the weak carbonate bond between the PABA and paclitaxel; however, this disadvantage was overcome by introducing a carbamate bond using an EDA linker in prodrugs 4 and 5. Thus, the incorporation of an EDA linker increased both the stability and PSA-mediated activation of these prodrugs. The cytotoxicity of each prodrug, as compared to paclitaxel, was determined against a variety of cell lines, including the PSA-secreting CWR22Rv1 prostate cancer cell line. The EDA-derived prodrug of paclitaxel 5 was stable and capable of being efficiently converted to an active drug that killed cells specifically in the presence of PSA, suggesting that this prodrug and similarly designed PSA-cleavable prodrugs may have potential as prostate cancer-specific therapeutic agents.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Solutions
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0968-0896
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4973-84
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pubmed:meshHeading |
pubmed-meshheading:17502149-Buffers,
pubmed-meshheading:17502149-Cell Line, Tumor,
pubmed-meshheading:17502149-Cell Proliferation,
pubmed-meshheading:17502149-Culture Media, Serum-Free,
pubmed-meshheading:17502149-Humans,
pubmed-meshheading:17502149-Male,
pubmed-meshheading:17502149-Molecular Structure,
pubmed-meshheading:17502149-Paclitaxel,
pubmed-meshheading:17502149-Prodrugs,
pubmed-meshheading:17502149-Prostatic Neoplasms,
pubmed-meshheading:17502149-Solutions,
pubmed-meshheading:17502149-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
Modulating paclitaxel bioavailability for targeting prostate cancer.
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pubmed:affiliation |
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, 1650 Orleans Street, Baltimore, MD 21231, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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