Preparation and affinity identification of glutamic acid-urea small molecule analogs in prostate cancer

Zhang,Zhiwei; Zhu,Zheng; Yang,Deyong; Fan,Weiwei; Wang,Jianbo; Li,Xiancheng; Chen,Xiaochi; Wang,Qifeng; Song,Xishuang

doi:10.3892/ol.2016.4699

Preparation and affinity identification of glutamic acid-urea small molecule analogs in prostate cancer

Authors:
- Zhiwei Zhang
- Zheng Zhu
- Deyong Yang
- Weiwei Fan
- Jianbo Wang
- Xiancheng Li
- Xiaochi Chen
- Qifeng Wang
- Xishuang Song
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Affiliations: Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Department of Urology, Dalian Medical University, Dalian, Liaoning 116085, P.R. China
Published online on: June 10, 2016 https://doi.org/10.3892/ol.2016.4699
Pages: 1001-1006

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Abstract

In recent years, study concerning activity inhibitors of prostate-specific membrane antigen (PSMA) has been concentrated on the glutamic urea (Glu-urea-R) small molecule and its analogs. The present study aimed to synthesize 4 analogs of Glu‑urea‑R and identify the affinities of these compounds to PSMA. The compounds were synthesized from raw materials, and the experimental procedures of the present study were in accordance with standard techniques under anhydrous and anaerobic conditions. Glu‑urea-Lysine (Glu-urea-Lys), Glu-urea-Ornithine (Glu-urea-Orn), Glu-urea-Glutamine (Glu-urea-Gln) and Glu‑urea‑Asparagine (Glu‑urea‑Asn) were successfully synthesized, and their structures were confirmed to be as desired using nuclear magnetic resonance spectroscopy and mass spectrometry. An affinity assay was performed to detect the affinity between the various compounds and PSMA expressed from the prostate cancer LNCap cell line. Glu‑urea‑Gln had the highest affinity to PSMA, followed by Glu‑urea‑Asn, Glu‑urea‑Orn and Glu‑urea‑Lys. In conclusion, the present study demonstrated that Glu‑urea‑R specifically binds PSMA expressed in the LNCap cell line and inhibits its activity.

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