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Affinity of Prostate Specific Membrane Antigen for Synthetic N‐Acetylaspartylglutamate Derivatives
Author(s) -
Javed Kainaat,
Cardona Lucia Salamanca,
Keshari Kayvan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.627.1
Subject(s) - glutamate carboxypeptidase ii , prostate cancer , chemistry , prostate , biochemistry , derivative (finance) , glutamate receptor , antigen , cancer , microbiology and biotechnology , cancer research , medicine , biology , receptor , immunology , financial economics , economics
Prostate Cancer is the most common non‐cutaneous malignancy affecting men in North America. Prostate Specific Membrane Antigen (PSMA) is a transmembrane protein present in normal prostate tissue. In malignant tissue PSMA is overexpressed and has been used as a marker for cancer. PSMA catalytically cleaves Acetylaspartylglutamate (NAAG) into acetyl‐aspartate and glutamate. It is well known that in prostate cancer the pool of glutamate is increased. It is hypothesized that the over expression of PSMA is responsible for the increase in glutamate in prostate cancer. Therefore, if a probe is created that is similar to NAAG and it is cleaved by PSMA, the products can be followed through their metabolic pathways and cancerous cells can be identified. The Keshari lab at Memorial Sloan Kettering Cancer Center (MSKCC) created three such NAAG‐derivative probes that incorporated either benzoic acid, oxalic acid or lactate in their structure instead of acetyl aspartate. The aim of this summer project was to determine the affinity of PSMA for the NAAG‐derivative probes compared to NAAG. To address this question pure PSMA was incubated with NAAG or NAAG‐derivative probes and enzyme activity was determined using an o‐phthadialdehyde fluorescent assay. The results of the experiment were that the NAAG‐derivative probes that incorporated benzoic acid or lactate are not cleaved by PSMA but the NAAG‐derivative probe containing oxalic acid is. In summary, only the oxalic acid NAAG‐derivative probe can serve as a substitute for NAAG and PSMA's affinity for this probe is about half of what it is for NAAG.This is the reaction that occurs when PSMA acts on its normal substrate, NAAG.