Design of a MCoTI-Based Cyclotide with Angiotensin (1-7)-Like Activity.
Design of a MCoTI-Based Cyclotide with Angiotensin (1-7)-Like Activity.
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DOI：
10.3390/molecules21020152
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发表时间：
2016-01-26
期刊：
影响因子：
--
通讯作者：
Camarero JA
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文献类型：
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作者：
Aboye T;Meeks CJ;Majumder S;Shekhtman A;Rodgers K;Camarero JA
我们首次报道了一种新型环肽的设计和合成，该环肽能够激活血管紧张素 (1-7) (AT1-7) 的独特受体，即 MAS1 受体。这是通过使用异肽键将 AT1-7 肽类似物移植到环肽 MCoTI-I 的环 6 上以保留活性所需的 AT1-7 的 α-氨基和 C 末端羧酸基团来实现的。所得环肽构建体能够采用环肽样构象，并表现出与 AT1-7 相似的活性。这种环肽在人血清中也表现出高稳定性，从而为设计一种新型的基于肽的癌症和心肌梗塞治疗提供了一种有前景的先导化合物。
We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the α-amino and C-terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction.