Inhibition of HIV-1 by a Peptide Ligand of the Genomic RNA Packaging Signal Ψ
Autor: | Jan Ferner, Julia Dietz, Manuel Grez, Yves Mély, Gilles Divita, Norbert Bannert, Harald Schwalbe, Stefan Stein, Lars Möller, Chinnappan Raja, Joachim Koch, Robert Tampé, Anette Pustowka, Ajit Kaur, Sarah Mensch, Ursula Dietrich |
---|---|
Rok vydání: | 2008 |
Předmět: |
Phage display
Anti-HIV Agents viruses Molecular Sequence Data Gene Products gag Peptide Genome Viral Biology Biochemistry Genome Virus Cell Line Transduction (genetics) Drug Discovery Humans Amino Acid Sequence General Pharmacology Toxicology and Pharmaceutics Pharmacology chemistry.chemical_classification Virus Assembly Organic Chemistry RNA Virus Release Capsid chemistry HIV-1 RNA Viral Molecular Medicine Peptides |
Zdroj: | ChemMedChem. 3:749-755 |
ISSN: | 1860-7187 1860-7179 |
Popis: | The interaction of the nucleocapsid NCp7 of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein with the RNA packaging signal Psi ensures specific encapsidation of the dimeric full length viral genome into nascent virus particles. Being an essential step in the HIV-1 replication cycle, specific genome encapsidation represents a promising target for therapeutic intervention. We previously selected peptides binding to HIV-1 Psi-RNA or stem loops (SL) thereof by phage display. Herein, we describe synthesis of peptide variants of the consensus HWWPWW motif on membrane supports to optimize Psi-RNA binding. The optimized peptide, psi-pepB, was characterized in detail with respect to its conformation and binding properties for the SL3 of the Psi packaging signal by NMR and tryptophan fluorescence quenching. Functional analysis revealed that psi-pepB caused a strong reduction of virus release by infected cells as monitored by reduced transduction efficiencies, capsid p24 antigen levels, and electron microscopy. Thus, this peptide shows antiviral activity and could serve as a lead compound to develop new drugs targeting HIV-1. |
Databáze: | OpenAIRE |
Externí odkaz: |