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.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90033, United States.
authors.forename: Teshome L
authors.initials: TL
authors.lastname: Aboye
authors.forename: Helen
authors.initials: H
authors.lastname: Ha
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Majumder
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Alexander
authors.initials: A
authors.lastname: Shekhtman
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
authors.forename: Julio A
authors.initials: JA
authors.lastname: Camarero
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D047169:Cyclotides / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: D019380:Anti-HIV Agents; C527276:CXCR4 protein, human; D047169:Cyclotides; D019718:Receptors, CXCR4