Synthesis and biological activity of peptide proline-boronic acids as proteasome inhibitors
Synthesis and biological activity of peptide proline-boronic acids as proteasome inhibitors
复制标题
蛋白酶体抑制剂肽脯氨酸硼酸的合成及其生物活性
DOI：
10.1016/j.bmc.2017.05.049
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发表时间：
2017-08-01
影响因子：
3.5
通讯作者：
Li, Runtao
中科院分区：
文献类型：
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作者：
Han, Liqiang;Wen, Yanzhao;Li, Runtao
在脯氨酸硼酸作为药效团在激酶抑制剂中的应用以及我们前期的研究成果的基础上，以脯氨酸硼酸为弹头，设计合成了二肽脯氨酸硼酸（I）和三肽脯氨酸硼酸（II）两个系列的肽脯氨酸硼酸。首先评估所有合成的化合物对MGC803细胞的生物活性，然后选择最好的化合物II-7来测试其对六种人肿瘤细胞系的抗肿瘤谱和对三个亚基的蛋白酶体抑制。结果表明，系列II比系列I具有更好的生物活性。化合物II-7不仅在细胞和蛋白酶体模型中表现出优异的生物活性，IC50值为nM水平，而且具有更好的亚基选择性。因此，以脯氨酸硼酸为弹头设计蛋白酶体抑制剂是合理的。 (C) 2017 Elsevier Ltd. 保留所有权利。
On the basis of the application of proline-boronic acid as pharmacophore in the kinase inhibitors and our previous research results, using proline-boronic acid as warhead, two series of peptide proline-boronic acids, dipeptide proline-boronic acids (I) and tripeptide proline-boronic acids (II), were designed and synthesized. All the synthesized compounds were first evaluated for their biological activity against MGC803 cell, and then, the best compound II-7 was selected to test its anti-tumor spectrum on six human tumor cell lines and proteasome inhibition against three subunits. The results indicated that series II have much better biological activities than series I. The compound II-7 exhibited not only excellent biological activities with IC50 values of nM level in both cell and proteasome models, but also much better subunit selectivity. Thus, proline-boronic acid as warhead is reasonable in the design of proteasome inhibitors. (C) 2017 Elsevier Ltd. All rights reserved.