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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2009-7-15
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pubmed:abstractText |
Prostate-specific antigen (PSA) is a serine protease biomarker that may play a role in prostate cancer development and progression. The inhibition of PSA's enzymatic activity with small molecule inhibitors is an attractive and, as of yet, unexploited target. Previously, we reported a series of peptidyl aldehyde and boronic acid based inhibitors of PSA. In this study, the structural requirements in the P2 and P3 positions of peptide-based PSA inhibitors are explored through the substitution of a series of natural and unnatural amino acids in these positions. This analysis demonstrated a preference for hydrophobic residues in the P2 position and amino acids with the potential to hydrogen bond in the P3 position. Using this information, a peptide boronic acid inhibitor with the sequence Cbz-Ser-Ser-Gln-Nle-(boro)-Leu was identified with a K(i) for PSA of 25nM. The attachment of a bulky metal chelating group to the amino terminal of this peptide did not adversely affect PSA inhibition. This result suggests that a platform of PSA inhibitor chelates could be developed as SPECT or PET-based imaging agents for prostate cancer.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-10077646,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-10485450,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-11391681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-11406537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-11507037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-11735417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-12057920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-12401085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-12444786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-12951170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-14994368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-15604294,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-16001455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-16189816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-1703033,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-17143882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-1716536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-17569629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-17894328,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-18297660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-18635003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-2422647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-3902893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-8034638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541487-9354459
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1464-3391
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4888-93
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:19541487-Amino Acid Sequence,
pubmed-meshheading:19541487-Boronic Acids,
pubmed-meshheading:19541487-Diagnostic Imaging,
pubmed-meshheading:19541487-Humans,
pubmed-meshheading:19541487-Male,
pubmed-meshheading:19541487-Peptide Library,
pubmed-meshheading:19541487-Peptides,
pubmed-meshheading:19541487-Prostate-Specific Antigen,
pubmed-meshheading:19541487-Prostatic Neoplasms,
pubmed-meshheading:19541487-Semen,
pubmed-meshheading:19541487-Substrate Specificity
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pubmed:year |
2009
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pubmed:articleTitle |
Optimization of peptide-based inhibitors of prostate-specific antigen (PSA) as targeted imaging agents for prostate cancer.
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pubmed:affiliation |
Department of Pharmacology and Molecular Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 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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