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

doi:10.1021/jm301468k

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 journal › Article › peer-review

121 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 language	English (US)
Pages (from-to)	10729-10734
Number of pages	6
Journal	Journal of medicinal chemistry
Volume	55
Issue number	23
DOIs	https://doi.org/10.1021/jm301468k
State	Published - Dec 13 2012
Externally published	Yes

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SDG 3 Good Health and Well-being

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title = "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.",

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language = "English (US)",

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T1 - Design of a novel cyclotide-based CXCR4 antagonist with anti-human immunodeficiency virus (HIV)-1 activity

AU - Aboye, Teshome L.

AU - Ha, Helen

AU - Majumder, Subhabrata

AU - Christ, Frauke

AU - Debyser, Zeger

AU - Shekhtman, Alexander

AU - Neamati, Nouri

AU - Camarero, Julio A.

PY - 2012/12/13

Y1 - 2012/12/13

N2 - 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.

AB - 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.

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JO - Journal of medicinal chemistry

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IS - 23

ER -

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

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