Design of a novel cyclotide-based CXCR4 antagonist with anti-human immunodeficiency virus (HIV)-1 activity

Teshome L. Aboye, Helen Ha, Subhabrata Majumder, Frauke Christ, Zeger Debyser, Alexander Shekhtman, Nouri Neamati, Julio A. Camarero

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

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 ≈ 20 nM) and an efficient HIV-1 cell-entry blocker (EC50 ≈ 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.

Original languageEnglish (US)
Pages (from-to)10729-10734
Number of pages6
JournalJournal of medicinal chemistry
Volume55
Issue number23
DOIs
StatePublished - Dec 13 2012

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