Zhang Zhiwei, Zhu Zheng, Yang Deyong, Fan Weiwei, Wang Jianbo, Li Xiancheng, Chen Xiaochi, Wang Qifeng, Song Xishuang
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.
Oncol Lett. 2016 Aug;12(2):1001-1006. doi: 10.3892/ol.2016.4699. Epub 2016 Jun 10.
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.
近年来，关于前列腺特异性膜抗原（PSMA）活性抑制剂的研究主要集中在谷氨酸尿素（Glu-urea-R）小分子及其类似物上。本研究旨在合成4种Glu-urea-R类似物，并确定这些化合物与PSMA的亲和力。化合物由原料合成，本研究的实验步骤符合无水和无氧条件下的标准技术。成功合成了谷氨酸尿素-赖氨酸（Glu-urea-Lys）、谷氨酸尿素-鸟氨酸（Glu-urea-Orn）、谷氨酸尿素-谷氨酰胺（Glu-urea-Gln）和谷氨酸尿素-天冬酰胺（Glu-urea-Asn），并使用核磁共振光谱和质谱确认其结构符合预期。进行亲和力测定以检测各种化合物与前列腺癌LNCap细胞系表达的PSMA之间的亲和力。Glu-urea-Gln对PSMA的亲和力最高，其次是Glu-urea-Asn、Glu-urea-Orn和Glu-urea-Lys。总之，本研究表明Glu-urea-R特异性结合LNCap细胞系中表达的PSMA并抑制其活性。
