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

106 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1021/jm301468k

Find It

Find It at U of M Libraries

Cite this

@article{a69599730889473cb2894466304e73d8,

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.",

author = "Aboye, {Teshome L.} and Helen Ha and Subhabrata Majumder and Frauke Christ and Zeger Debyser and Alexander Shekhtman and Nouri Neamati and Camarero, {Julio A.}",

year = "2012",

month = dec,

day = "13",

doi = "10.1021/jm301468k",

language = "English (US)",

volume = "55",

pages = "10729--10734",

journal = "Journal of medicinal chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "23",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=84871019068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871019068&partnerID=8YFLogxK

U2 - 10.1021/jm301468k

DO - 10.1021/jm301468k

M3 - Article

C2 - 23151033

AN - SCOPUS:84871019068

SN - 0022-2623

VL - 55

SP - 10729

EP - 10734

JO - Journal of medicinal chemistry

JF - Journal of medicinal chemistry

IS - 23

ER -

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

Abstract

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this