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

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2012 Nov 16

PMID 23151033

Citations 53

Authors

Teshome L Aboye

Helen Ha

Subhabrata Majumder

Frauke Christ

Zeger Debyser

Alexander Shekhtman

Nouri Neamati

Julio A Camarero

Affiliations

Soon will be listed here.

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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