glutamate carboxypeptidase ii


Summary: A metallocarboxypeptidase that is predominantly expressed as a membrane-bound enzyme. It catalyzes the hydrolysis of an unsubstituted, C-terminal glutamyl residue, typically from PTEROYLPOLYGLUTAMIC ACIDS. It was formerly classified as EC

Top Publications

  1. Mannweiler S, Amersdorfer P, Trajanoski S, Terrett J, King D, Mehes G. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res. 2009;15:167-72 pubmed publisher
    ..Our findings clearly support the feasibility but also direct to potential failures of PSMA-targeted in vivo diagnostic and therapeutic approaches in prostate cancer patients with distant metastasis. ..
  2. Zhou J, Neale J, Pomper M, Kozikowski A. NAAG peptidase inhibitors and their potential for diagnosis and therapy. Nat Rev Drug Discov. 2005;4:1015-26 pubmed
  3. Zhong C, Zhao X, Van K, Bzdega T, Smyth A, Zhou J, et al. NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat. J Neurochem. 2006;97:1015-25 pubmed
    ..The results are consistent with the hypothesis that inhibition of NAAG peptidase may reduce excitotoxic events associated with TBI. ..
  4. Waeckerle Men Y, Uetz von Allmen E, Fopp M, von Moos R, Böhme C, Schmid H, et al. Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma. Cancer Immunol Immunother. 2006;55:1524-33 pubmed
    ..DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses. ..
  5. Majer P, Hin B, Stoermer D, Adams J, Xu W, Duvall B, et al. Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain. J Med Chem. 2006;49:2876-85 pubmed
    ..a benzyl moiety at the P1' position have been synthesized and tested for their abilities to inhibit glutamate carboxypeptidase II (GCP II)...
  6. Bacich D, Wozniak K, Lu X, O Keefe D, Callizot N, Heston W, et al. Mice lacking glutamate carboxypeptidase II are protected from peripheral neuropathy and ischemic brain injury. J Neurochem. 2005;95:314-23 pubmed
    ..A new strategy for the treatment of neuronal injury involves inhibition of the neuropeptidase glutamate carboxypeptidase II (GCP II), also known as N-acetylated alpha-linked acidic dipeptidase...
  7. SCHULKE N, Varlamova O, Donovan G, Ma D, Gardner J, Morrissey D, et al. The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proc Natl Acad Sci U S A. 2003;100:12590-5 pubmed
    ..These findings on PSMA structure and biology may have important implications for active and passive immunotherapy of prostate and other cancers. ..
  8. Zhang W, Murakawa Y, Wozniak K, Slusher B, Sima A. The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy. J Neurol Sci. 2006;247:217-23 pubmed
    ..One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase)...
  9. Ghose S, Chin R, Gallegos A, Roberts R, Coyle J, Tamminga C. Localization of NAAG-related gene expression deficits to the anterior hippocampus in schizophrenia. Schizophr Res. 2009;111:131-7 pubmed publisher
    ..b>Glutamate carboxypeptidase II (GCPII), an enzyme that metabolizes NAAG, is also implicated in this illness...

More Information


  1. Ray Banerjee S, Pullambhatla M, Foss C, Falk A, Byun Y, Nimmagadda S, et al. Effect of chelators on the pharmacokinetics of (99m)Tc-labeled imaging agents for the prostate-specific membrane antigen (PSMA). J Med Chem. 2013;56:6108-21 pubmed publisher
    ..These results suggest that choice of chelator is an important pharmacokinetic consideration in the development of (99m)Tc-labeled radiopharmaceuticals targeting PSMA. ..
  2. Hillier S, Maresca K, Femia F, Marquis J, Foss C, Nguyen N, et al. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res. 2009;69:6932-40 pubmed publisher
    ..PSMA-specific radiopharmaceuticals should provide a novel molecular targeting option for the detection and staging of prostate cancer. ..
  3. Cho S, Gage K, Mease R, Senthamizhchelvan S, Holt D, Jeffrey Kwanisai A, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med. 2012;53:1883-91 pubmed publisher
    ..This study also provides dose estimates for (18)F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as (18)F-FDG. ..
  4. Dassie J, Liu X, Thomas G, Whitaker R, Thiel K, Stockdale K, et al. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol. 2009;27:839-49 pubmed publisher
    ..Anti-tumor activity was further enhanced by appending a polyethylene glycol moiety, which increased the chimeras' circulating half-life. ..
  5. van der Post J, de Visser S, de Kam M, Woelfler M, Hilt D, Vornov J, et al. The central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693. Br J Clin Pharmacol. 2005;60:128-36 pubmed
    ..Comcomitant food intake reduced C(max) and AUC. CNS effects and GI AEs increased in incidence over placebo only at the 1125 mg dose. ..
  6. Liu T, Wu L, Kazak M, Berkman C. Cell-Surface labeling and internalization by a fluorescent inhibitor of prostate-specific membrane antigen. Prostate. 2008;68:955-64 pubmed publisher
    ..Our results suggest that potent, small-molecule inhibitors of PSMA can be utilized as carriers for targeted delivery for prostate cancer for future imaging and therapeutic applications. ..
  7. Schmittgen T, Teske S, Vessella R, True L, Zakrajsek B. Expression of prostate specific membrane antigen and three alternatively spliced variants of PSMA in prostate cancer patients. Int J Cancer. 2003;107:323-9 pubmed
    ..We note increased PSMA expression in some malignant tissues, however, these increases are modest in magnitude. We also report that the expression of a novel splice variant, PSM-D, is elevated in prostate cancer metastases. ..
  8. Ghosh A, Heston W. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91:528-39 pubmed
    ..In this review we have discussed the regulation of PSMA expression within the cells, and significance of its expression in prostate cancer and metastasis. ..
  9. Cao K, Mao X, Wang D, Xu L, Yuan G, Dai S, et al. High expression of PSM-E correlated with tumor grade in prostate cancer: a new alternatively spliced variant of prostate-specific membrane antigen. Prostate. 2007;67:1791-800 pubmed
    ..229, P = 0.057). PSM-E may be a potential prognostic indicator for PCa progression and may be a new target antigen for therapy of PCa. ..
  10. Chandran S, Banerjee S, Mease R, Pomper M, Denmeade S. Characterization of a targeted nanoparticle functionalized with a urea-based inhibitor of prostate-specific membrane antigen (PSMA). Cancer Biol Ther. 2008;7:974-82 pubmed
    ..Ongoing in vivo studies address the localization, activity and toxicity of these targeted nanoparticles against PSMA-producing human prostate tumor xenografts. ..
  11. Zhao W, Xu Y, Kong D, Liu R, Zhang Z, Jin C, et al. Tissue-selective RNA interference in prostate cancer cell using prostate specific membrane antigen promoter/enhancer. Urol Oncol. 2009;27:539-47 pubmed publisher
    ..Suppression of STAT3 by using this system decreased proliferation and induced apoptosis of PC-3 and LNCaP cells. This system may be useful for RNAi therapy for prostate cancer. ..
  12. Barinka C, Mlcochova P, Sácha P, Hilgert I, Majer P, Slusher B, et al. Amino acids at the N- and C-termini of human glutamate carboxypeptidase II are required for enzymatic activity and proper folding. Eur J Biochem. 2004;271:2782-90 pubmed
    Human glutamate carboxypeptidase II (GCPII) is a co-catalytic metallopeptidase and its putative catalytic domain is homologous to the aminopeptidases from Vibrio proteolyticus and Streptomyces griseus...
  13. Neale J, Olszewski R, Gehl L, Wroblewska B, Bzdega T. The neurotransmitter N-acetylaspartylglutamate in models of pain, ALS, diabetic neuropathy, CNS injury and schizophrenia. Trends Pharmacol Sci. 2005;26:477-84 pubmed
    ..In this review, we summarize recent studies in these animal models and discuss the mechanisms by which NAAG peptidase inhibitors achieve these effects. ..
  14. Ikegami S, Tadakuma T, Ono T, Suzuki S, Yoshimura I, Asano T, et al. Treatment efficiency of a suicide gene therapy using prostate-specific membrane antigen promoter/enhancer in a castrated mouse model of prostate cancer. Cancer Sci. 2004;95:367-70 pubmed
  15. Fuessel S, Meye A, Schmitz M, Zastrow S, Linne C, Richter K, et al. Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. Prostate. 2006;66:811-21 pubmed
    ..The application of a peptide cocktail-derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa. ..
  16. Barwe S, Maul R, Christiansen J, Anilkumar G, Cooper C, Kohn D, et al. Preferential association of prostate cancer cells expressing prostate specific membrane antigen to bone marrow matrix. Int J Oncol. 2007;30:899-904 pubmed
    ..This phenomenon occurs via activation of focal adhesion kinase and provides the first evidence of a link between PSMA expression and prostate cancer metastasis to the bone. ..
  17. Neale J, Olszewski R, Zuo D, Janczura K, Profaci C, Lavin K, et al. Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family. J Neurochem. 2011;118:490-8 pubmed publisher
  18. Long J, Yourick D, Slusher B, Robinson M, Meyerhoff J. Inhibition of glutamate carboxypeptidase II (NAALADase) protects against dynorphin A-induced ischemic spinal cord injury in rats. Eur J Pharmacol. 2005;508:115-22 pubmed
    ..These results indicate that 2-PMPA provides effective protection against excitotoxic spinal cord injury. ..
  19. Barinka C, Rojas C, Slusher B, Pomper M. Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer. Curr Med Chem. 2012;19:856-70 pubmed
    b>Glutamate carboxypeptidase II (GCPII) is a membrane-bound binuclear zinc metallopeptidase with the highest expression levels found in the nervous and prostatic tissue...
  20. Adedoyin M, Vicini S, Neale J. Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model. Mol Pain. 2010;6:60 pubmed publisher
  21. Zhong C, Zhao X, Sarva J, Kozikowski A, Neale J, Lyeth B. NAAG peptidase inhibitor reduces acute neuronal degeneration and astrocyte damage following lateral fluid percussion TBI in rats. J Neurotrauma. 2005;22:266-76 pubmed
    ..05). We conclude that the NAAG peptidase inhibitor ZJ-43 is a potential novel strategy to reduce both neuronal and astrocyte damage associated with the glutamate excitotoxicity after TBI. ..
  22. Chen Y, Foss C, Byun Y, Nimmagadda S, Pullambhatla M, Fox J, et al. Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer. J Med Chem. 2008;51:7933-43 pubmed publisher
    ..Because of the many radiohalogenated moieties that can be attached via the epsilon amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer. ..
  23. Hillier S, Maresca K, Lu G, Merkin R, Marquis J, Zimmerman C, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med. 2013;54:1369-76 pubmed publisher
    ..These (99m)Tc-labeled radiopharmaceuticals targeting PSMA may provide a SPECT molecular imaging option to assist in the initial diagnosis of prostate cancer and the management of patient care by monitoring disease progression. ..
  24. Wu L, Anderson M, Toriyabe Y, Maung J, Campbell T, Tajon C, et al. The molecular pruning of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen. Bioorg Med Chem. 2007;15:7434-43 pubmed
    ..86 nM to 4.1 microM. Computational docking, utilizing a recently solved X-ray crystal structure of the recombinant protein, along with enzyme inhibition data, was used to propose a pharmacophore model for the PSMA active site. ..
  25. Wozniak K, Rojas C, Wu Y, Slusher B. The role of glutamate signaling in pain processes and its regulation by GCP II inhibition. Curr Med Chem. 2012;19:1323-34 pubmed
    ..GCPII (glutamate carboxypeptidase II) cleaves the prevalent neuropeptide NAAG into NAA and glutamate and there is widespread evidence and ..
  26. Olszewski R, Bukhari N, Zhou J, Kozikowski A, Wroblewski J, Shamimi Noori S, et al. NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR. J Neurochem. 2004;89:876-85 pubmed
    ..This novel compound is a potent inhibitor of enzymes, glutamate carboxypeptidase II (K(i) = 0.8 nM) and III (K(i) = 23 nM) that deactivate NAAG following synaptic release...
  27. Alt K, Wiehr S, Ehrlichmann W, Reischl G, Wolf P, Pichler B, et al. High-resolution animal PET imaging of prostate cancer xenografts with three different 64Cu-labeled antibodies against native cell-adherent PSMA. Prostate. 2010;70:1413-21 pubmed publisher
    ..Due to the high and specific uptake of the 64Cu-labeled mAbs in PSMA-positive tumors, these antibodies represent excellent tools for prostate cancer imaging. ..
  28. Evans M, Smith Jones P, Wongvipat J, Navarro V, Kim S, Bander N, et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc Natl Acad Sci U S A. 2011;108:9578-82 pubmed publisher
  29. Maung J, Mallari J, Girtsman T, Wu L, Rowley J, Santiago N, et al. Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates. Bioorg Med Chem. 2004;12:4969-79 pubmed
  30. Kuroda K, Liu H, Kim S, Guo M, Navarro V, Bander N. Docetaxel down-regulates the expression of androgen receptor and prostate-specific antigen but not prostate-specific membrane antigen in prostate cancer cell lines: implications for PSA surrogacy. Prostate. 2009;69:1579-85 pubmed publisher
  31. Barinka C, Byun Y, Dusich C, Banerjee S, Chen Y, Castanares M, et al. Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization. J Med Chem. 2008;51:7737-43 pubmed publisher
    Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer...
  32. Haffner M, Kronberger I, Ross J, Sheehan C, Zitt M, Mühlmann G, et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol. 2009;40:1754-61 pubmed publisher
    ..Because of its highly tumor-restricted expression and its accessibility to targeted therapy, PSMA represents a promising therapeutic and diagnostic target in colorectal and gastric cancer. ..
  33. Mhawech Fauceglia P, Smiraglia D, Bshara W, Andrews C, Schwaller J, South S, et al. Prostate-specific membrane antigen expression is a potential prognostic marker in endometrial adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2008;17:571-7 pubmed publisher
  34. Vittes G, Harden E, Ottensmeier C, Rice J, Stevenson F. DNA fusion gene vaccines induce cytotoxic T-cell attack on naturally processed peptides of human prostate-specific membrane antigen. Eur J Immunol. 2011;41:2447-56 pubmed publisher
    ..The preclinical model provides a powerful tool for generating CD8(+) T cells able to predict whether target cells can process and present peptides, essential for planning peptide vaccine-based clinical trials. ..
  35. Ghosh A, Heston W. Effect of carbohydrate moieties on the folate hydrolysis activity of the prostate specific membrane antigen. Prostate. 2003;57:140-51 pubmed
    ..Removal of sugars partially or completely causes PSMA to be enzymatically inactive, improperly folded, resulting in increased rate of degradation. ..
  36. Kozela E, Wrobel M, Kos T, Wojcikowski J, Daniel W, Wozniak K, et al. 2-MPPA, a selective glutamate carboxypeptidase II inhibitor, attenuates morphine tolerance but not dependence in C57/Bl mice. Psychopharmacology (Berl). 2005;183:275-84 pubmed
    ..The present findings suggest complex effects of GCP II inhibition on morphine dependence and tolerance and imply a role of mGluR II in the actions of 2-MPPA. ..
  37. Mesters J, Barinka C, Li W, Tsukamoto T, Majer P, Slusher B, et al. Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer. EMBO J. 2006;25:1375-84 pubmed
    Membrane-bound glutamate carboxypeptidase II (GCPII) is a zinc metalloenzyme that catalyzes the hydrolysis of the neurotransmitter N-acetyl-L-aspartyl-L-glutamate (NAAG) to N-acetyl-L-aspartate and L-glutamate (which is itself a ..
  38. Rajasekaran A, Anilkumar G, Christiansen J. Is prostate-specific membrane antigen a multifunctional protein?. Am J Physiol Cell Physiol. 2005;288:C975-81 pubmed
    ..Insights into the possible functions of PSMA should improve the diagnostic and therapeutic values of this clinically important molecule. ..
  39. Barinka C, Sácha P, Sklenar J, Man P, Bezouska K, Slusher B, et al. Identification of the N-glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity. Protein Sci. 2004;13:1627-35 pubmed
    b>Glutamate carboxypeptidase II (GCPII) is a membrane peptidase expressed in the prostate, central and peripheral nervous system, kidney, small intestine, and tumor-associated neovasculature...
  40. Farokhzad O, Jon S, Khademhosseini A, Tran T, LaVan D, Langer R. Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer cells. Cancer Res. 2004;64:7668-72 pubmed
    ..To our knowledge, this represents the first report of targeted drug delivery with nanoparticle-aptamer bioconjugates. ..
  41. Ben Jemaa A, Bouraoui Y, Sallami S, Banasr A, Ben Rais N, Ouertani L, et al. Co-expression and impact of prostate specific membrane antigen and prostate specific antigen in prostatic pathologies. J Exp Clin Cancer Res. 2010;29:171 pubmed publisher
    ..With regard to the duality PSMA-PSA, this implies the significance of their investigation together in normal and pathologic prostate tissues. ..
  42. Yao V, Berkman C, Choi J, O Keefe D, Bacich D. Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. Prostate. 2010;70:305-16 pubmed publisher
    ..These findings implicate PSMA in both the metabolism of polyglutamated folates, and in the uptake of monoglutamated folates. Under conditions of LF or PF levels, PSMA gives cells expressing it a proliferative advantage. ..
  43. Thomas A, Wozniak K, Tsukamoto T, Calvin D, Wu Y, Rojas C, et al. Glutamate carboxypeptidase II (NAALADase) inhibition as a novel therapeutic strategy. Adv Exp Med Biol. 2006;576:327-37; discussion 361-3 pubmed
    ..GCP II inhibition may represent a novel glutamate regulating strategy devoid of the side effects that have hampered the development of postsynaptic glutamate receptor antagonists. ..
  44. Banerjee S, Foss C, Castanares M, Mease R, Byun Y, Fox J, et al. Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J Med Chem. 2008;51:4504-17 pubmed publisher
    ..PSMA can accommodate the steric requirements of (99m)Tc/Re complexes within PSMA inhibitors, the best results achieved with a linker moiety between the epsilon amine of the urea lysine and the chelator...
  45. Wang K, Gao X, Pang J, Liu X, Cai Y, Zhang Y, et al. Dendritic cells transduced with a PSMA-encoding adenovirus and cocultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against prostate cancer cells. Urol Oncol. 2009;27:26-32 pubmed publisher
    ..Therefore, this approach may have a potential for an adoptive immunotherapy for patients with advanced PCa. ..
  46. Mlcochova P, Plechanovova A, Barinka C, Mahadevan D, Saldanha J, Rulísek L, et al. Mapping of the active site of glutamate carboxypeptidase II by site-directed mutagenesis. FEBS J. 2007;274:4731-41 pubmed
    Human glutamate carboxypeptidase II [GCPII (EC] is recognized as a promising pharmacological target for the treatment and imaging of various pathologies, including neurological disorders and prostate cancer...
  47. Low L, Mander A, McCann K, Dearnaley D, Tjelle T, Mathiesen I, et al. DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer. Hum Gene Ther. 2009;20:1269-78 pubmed publisher
    ..Responses persisted to 18 months of follow-up. These data establish EP as a potent method for stimulating humoral responses induced by DNA vaccination in humans. ..
  48. Yamamoto T, Saito O, Aoe T, Bartolozzi A, Sarva J, Zhou J, et al. Local administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in peripheral pain in rats. Eur J Neurosci. 2007;25:147-58 pubmed
  49. Zhang Y, Guo Z, Du T, Chen J, Wang W, Xu K, et al. Prostate specific membrane antigen (PSMA): a novel modulator of p38 for proliferation, migration, and survival in prostate cancer cells. Prostate. 2013;73:835-41 pubmed publisher
    ..These data suggests PSMA may stimulate prostate cancer cells proliferation, migration and survival through p38 MAPK pathway, revealing a novel mechanism for PSMA playing positive role on LNCaP cells. ..
  50. Fishman M. A changing world for DCvax: a PSMA loaded autologous dendritic cell vaccine for prostate cancer. Expert Opin Biol Ther. 2009;9:1565-75 pubmed publisher
    ..Further clinical trial development of DCvax-prostate is warranted, and required if it is to find a relevant clinical application. ..
  51. Lambert L, Mitchell S. Molecular evolution of the transferrin receptor/glutamate carboxypeptidase II family. J Mol Evol. 2007;64:113-28 pubmed
    ..Other family members include transferrin receptor 2 (TfR2), glutamate carboxypeptidase II (GCP2 or PSMA), N-acetylated alpha-linked acidic dipeptidase-like protein (NLDL), N-acetylated alpha-..
  52. Olszewski R, Wegorzewska M, Monteiro A, Krolikowski K, Zhou J, Kozikowski A, et al. Phencyclidine and dizocilpine induced behaviors reduced by N-acetylaspartylglutamate peptidase inhibition via metabotropic glutamate receptors. Biol Psychiatry. 2008;63:86-91 pubmed
  53. Tykvart J, Sacha P, Barinka C, Knedlík T, Starkova J, Lubkowski J, et al. Efficient and versatile one-step affinity purification of in vivo biotinylated proteins: expression, characterization and structure analysis of recombinant human glutamate carboxypeptidase II. Protein Expr Purif. 2012;82:106-15 pubmed publisher
    ..We optimized a protocol for large-scale expression and purification of AviTEV-tagged recombinant human glutamate carboxypeptidase II (Avi-GCPII) with milligram yields per liter of culture...
  54. Ghosh A, Wang X, Klein E, Heston W. Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness. Cancer Res. 2005;65:727-31 pubmed
    ..Finally, expression of PSMA mutants lacking carboxypeptidase activity reduced the impact of PSMA expression on invasiveness. Thus, it seems that the enzymatic activity is associated with the effect of PSMA on invasiveness. ..
  55. Milowsky M, Nanus D, Kostakoglu L, Sheehan C, Vallabhajosula S, Goldsmith S, et al. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol. 2007;25:540-7 pubmed
    ..Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent. ..
  56. Zhang L, Wang C, Yang R, Shi J, Fu R, Chen L, et al. Real-time quantitative RT-PCR assay of prostate-specific antigen and prostate-specific membrane antigen in peripheral blood for detection of prostate cancer micrometastasis. Urol Oncol. 2008;26:634-40 pubmed publisher
    ..This method improves accuracy and liability of assessment of disseminated prostate cancer cells in peripheral blood and is promising for clinical diagnosis purpose. ..
  57. Mease R, Foss C, Pomper M. PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr Top Med Chem. 2013;13:951-62 pubmed
    ..These early clinical results suggest that PET/CT using PSMA-targeted agents, especially with compounds of low molecular weight, will make valuable contributions to the management of PCa. ..
  58. Chen Y, Pullambhatla M, Foss C, Byun Y, Nimmagadda S, Senthamizhchelvan S, et al. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin Cancer Res. 2011;17:7645-53 pubmed publisher
    ..The bladder wall is the dose-limiting organ. These data suggest [(18)F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues. ..
  59. Bander N, Trabulsi E, Kostakoglu L, Yao D, Vallabhajosula S, Smith Jones P, et al. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J Urol. 2003;170:1717-21 pubmed
    ..Radiolabeled J591 accurately targets bone and soft tissue metastatic prostate cancer sites, and may be useful for targeting therapeutic and/or diagnostic imaging agents. ..
  60. Vornov J, Wozniak K, Wu Y, Rojas C, Rais R, Slusher B. Pharmacokinetics and pharmacodynamics of the glutamate carboxypeptidase II inhibitor 2-MPPA show prolonged alleviation of neuropathic pain through an indirect mechanism. J Pharmacol Exp Ther. 2013;346:406-13 pubmed publisher
    b>Glutamate carboxypeptidase II (GCP II) is a therapeutic target in neurologic disorders associated with excessive activation of glutamatergic systems...
  61. Anderson M, Wu L, Santiago N, Moser J, Rowley J, Bolstad E, et al. Substrate specificity of prostate-specific membrane antigen. Bioorg Med Chem. 2007;15:6678-86 pubmed
    ..Lastly, binding modes of endogenous substrates and our best synthetic substrate (4-phenylazobenzoyl-Glu-gamma-Glu) were proposed by computational docking studies into an X-ray crystal structure of the PSMA extracellular domain. ..
  62. Yamada T, Zuo D, Yamamoto T, Olszewski R, Bzdega T, Moffett J, et al. NAAG peptidase inhibition in the periaqueductal gray and rostral ventromedial medulla reduces flinching in the formalin model of inflammation. Mol Pain. 2012;8:67 pubmed publisher
  63. Afshar Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart H, Hadaschik B, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486-95 pubmed publisher
    ..Within healthy organs, kidneys and salivary glands demonstrated the highest radiotracer uptake. Lesions suspicious for PC presented with excellent contrast as early as 1 h p.i. with high detection rates even at low PSA levels. ..
  64. Kozikowski A, Zhang J, Nan F, Petukhov P, Grajkowska E, Wroblewski J, et al. Synthesis of urea-based inhibitors as active site probes of glutamate carboxypeptidase II: efficacy as analgesic agents. J Med Chem. 2004;47:1729-38 pubmed
    The neuropeptidase glutamate carboxypeptidase II (GCPII) hydrolyzes N-acetyl-L-aspartyl-L-glutamate (NAAG) to liberate N-acetylaspartate and glutamate...
  65. Ben Jemaa A, Sallami S, Ramarli D, Colombatti M, Oueslati R. The proinflammatory cytokine, IL-6, and its interference with bFGF signaling and PSMA in prostate cancer cells. Inflammation. 2013;36:643-50 pubmed publisher
    ..In developing novel therapeutic modalities targeting IL-6, significant attention should be given to PSMA and its inactivation to fight against prostate cancer. ..
  66. Hillier S, Kern A, Maresca K, Marquis J, Eckelman W, Joyal J, et al. 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med. 2011;52:1087-93 pubmed publisher
    ..The high specificity of (123)I-MIP-1072 for prostate cancer may allow monitoring of tumor progression in patients before, during, and after chemotherapy. ..
  67. Thomas A, ROJAS C, Hill J, Shaw M, Slusher B. Bioanalysis of N-acetyl-aspartyl-glutamate as a marker of glutamate carboxypeptidase II inhibition. Anal Biochem. 2010;404:94-6 pubmed publisher
    ..based on differences between glutamate concentrations before and after NAAG hydrolysis with exogenous glutamate carboxypeptidase II (GCP II) using high-performance liquid chromatography (HPLC) followed by fluorescence detection...
  68. Mhawech Fauceglia P, Zhang S, Terracciano L, Sauter G, Chadhuri A, Herrmann F, et al. Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using mutiple tumour tissue microarray technique. Histopathology. 2007;50:472-83 pubmed
    ..9% and 82.9%, respectively. Despite its expression by subsets of various types of malignancies, PSMA is still considered to be fairly sensitive and highly specific for PaC. ..
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