Design of a Novel Cyclotide-Based CXCR4 Antagonist with Anti-Human Immunodeficiency Virus (HIV)-1 Activity

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• 作者：Teshome L. Aboye ; Helen Ha ; Subhabrata Majumder ; Frauke Christ ; Zeger Debyser ; Alexander Shekhtman ; Nouri Neamati ; Julio A. Camarero
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：December 13, 2012
• 年：2012
• 卷：55
• 期：23
• 页码：10729-10734
• 全文大小：394K
• 年卷期：v.55,no.23(December 13, 2012)
• ISSN：1520-4804

文摘

Herein, we report for the first time the design and synthesis of a novel cyclotide able to efficiently inhibit HIV-1 viral replication by selectively targeting cytokine receptor CXCR4. This was accomplished by grafting a series of topologically modified CVX15 based peptides onto the loop 6 of cyclotide MCoTI-I. The most active compound produced in this study was a potent CXCR4 antagonist (EC₅₀ 鈮?20 nM) and an efficient HIV-1 cell-entry blocker (EC₅₀ 鈮?2 nM). 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 anticancer and anti-HIV-1 therapeutics.