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

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.

SUBMITTER: Aboye TL

PROVIDER: S-EPMC3521869 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Aboye Teshome L TL Ha Helen H Majumder Subhabrata S Christ Frauke F Debyser Zeger Z Shekhtman Alexander A Neamati Nouri N Camarero Julio A JA

Journal of medicinal chemistry 20121127 23

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 ...[more]

PMID: 23151033

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