Design, synthesis and biological evaluation of novel peptide MC2 analogues from Momordica charantia as potential anti-diabetic agents.
Design, synthesis and biological evaluation of novel peptide MC2 analogues from Momordica charantia as potential anti-diabetic agents.
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DOI：
10.1039/c5ob00333d
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发表时间：
2015-03
影响因子：
3.2
通讯作者：
Baowei Yang;Xue Li;Chenyu Zhang;Sijia Yan;Wei Wei-Wei;Xuekun Wang;Xin-Xian Deng;Hai Qian;
中科院分区：
文献类型：
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作者：
Baowei Yang;Xue Li;Chenyu Zhang;Sijia Yan;Wei Wei-Wei;Xuekun Wang;Xin-Xian Deng;Hai Qian;
设计、合成了3个系列的苦瓜（MC）2类似物，并对其抗高血压作用进行了评价。聚焦于肽MC 2的丙氨酸扫描表明残基脯氨酸（Pro）（3）、丝氨酸（Ser）（6）、异亮氨酸（Ile）（7）和Ser（10）对于抗高血糖作用的重要性。在第一系列的MC 2类似物中，肽I-4表现出更好的抗高血压作用，并被选择用于进一步修饰。通过用由谷氨酸-Xaa-赖氨酸（Glu-Xaa-Lys）支架和二脯氨酸片段组成的i -（i + 2）内酰胺桥扫描残基Pro（3）、Ser（6）、Ile（7）和Ser（10）来设计另外两个系列的构象约束的类似物。通过在正常小鼠和糖尿病小鼠中筛选，与I-4相比，肽II-1、II-2和III-3显示出抗高血压和抗氧化活性的显著改善。这些数据表明，II-1，II-2和III-3可能是未来治疗糖尿病的候选药物。
Three series of Momordica charantia (MC)2 analogues were designed, synthesized and evaluated for their anti-hyperglycaemic effects. Alanine scanning focusing on the peptide MC2 indicated the importance of the residues proline (Pro)(3), serine (Ser)(6), isoleucine (Ile)(7) and Ser(10) for anti-hyperglycaemic effects. Among the first series of MC2 analogues, peptide I-4 exhibited a better anti-hyperglycaemic effect and was chosen for further modification. A further two series of conformationally constrained analogues were designed by scanning the residues Pro(3), Ser(6), Ile(7), and Ser(10) with an i - (i + 2) lactam bridge consisting of a glutamic acid-Xaa-lysine (Glu-Xaa-Lys) scaffold and a diproline fragment. By screening in normal mice and mice with diabetes mellitus, peptides II-1, II-2 and III-3 showed a significant improvement in anti-hyperglycaemic and anti-oxidative activities compared with I-4. These data suggest that II-1, II-2 and III-3 could be candidates for future treatment of diabetes mellitus.