Abstract
Prostate-specific membrane antigen (PSMA) is an ideal biomarker for prostate cancer. A previously reported 2-5A conjugate RBI1033 (3) showed binding affinity more than 10 times higher than the parent urea-based compound (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (1). The purpose of this work is to further optimize the structure of 3 to identify highly selective ligands of PSMA. It was found that conjugates having 2-5A in their structure showed extraordinary improved binding affinity to PSMA compared with compound 1. Removal of 2-5A significantly reduced its biological activity. The results will provide a path to agents for targeted imaging and treatment of prostate cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenine Nucleotides / chemistry*
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Adenine Nucleotides / metabolism
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Adenine Nucleotides / pharmacology*
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Antigens, Surface
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Binding, Competitive
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Biological Transport
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Cell Line, Tumor
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Glutamate Carboxypeptidase II / antagonists & inhibitors*
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Humans
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Ligands
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Male
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Molecular Imaging
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Neoplasm Metastasis
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Oligoribonucleotides / chemistry*
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Oligoribonucleotides / metabolism
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Oligoribonucleotides / pharmacology*
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Prostatic Neoplasms / pathology
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Protease Inhibitors / chemistry*
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Protease Inhibitors / metabolism
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Protease Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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Adenine Nucleotides
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Antigens, Surface
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Ligands
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Oligoribonucleotides
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Protease Inhibitors
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2',5'-oligoadenylate
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FOLH1 protein, human
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Glutamate Carboxypeptidase II