Pseudoirreversible Inhibition of Prostate-Specific Membrane Antigen by Phosphoramidate Peptidomimetics
Pseudoirreversible Inhibition of Prostate-Specific Membrane Antigen by Phosphoramidate Peptidomimetics
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DOI：
10.1021/bi801883v
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发表时间：
2008-12-02
期刊：
影响因子：
2.9
通讯作者：
Berkman, Clifford E.
中科院分区：
文献类型：
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作者：
Liu, Tiancheng;Toriyabe, Yoko;Berkman, Clifford E.
通过抑制可逆性实验确定了前列腺特异性膜抗原的氨基磷酸酯模拟肽抑制剂的抑制模式。结果表明，这些抑制剂可以分为三类：假不可逆（化合物1-3），中度可逆（化合物4-9），和快速可逆的抑制剂（化合物10和11）。进一步评价来自每一类别的代表性化合物诱导PSMA的细胞内化的能力。这些实验的结果显示，假不可逆抑制剂1诱导最大的PSMA内化。假不可逆PSMA抑制剂的发现预计将为前列腺癌和神经系统疾病的研究和治疗应用提供新的途径。
The mode of inhibition for phosphoramidate peptidomimetic inhibitors of prostate-specific membrane antigen was determined by inhibition reversibility experiments. The results revealed that these inhibitors can be classified into three types: pseudoirreversible (compounds 1-3), moderately reversible (compounds 4-9), and rapidly reversible inhibitors (compounds 10 and 11). Representative compounds from each class were further evaluated for their ability to induce cellular internalization of PSMA. Results from these experiments revealed that the pseudoirreversible inhibitor 1 induced the greatest PSMA internalization. The discovery of pseudoirreversible PSMA inhibitors is expected to provide a new avenue of investigation and therapeutic applications for prostate cancer and neurological disorders.