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Journal/Book: ChemMedChem
Published: 2008
Pages: 749–755
Volume: 3
Accession no.: 152

Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal Psi.

Julia Dietz, Joachim Koch, Ajit Kaur, Chinnappan Raja, Stefan Stein, Manuel Grez, Anette Pustowka, Sarah Mensch, Jan Ferner, Lars Möller, Norbert Bannert, Robert Tampé, Gilles Divita, Yves Mély, Harald Schwalbe
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.
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Prof. Dr. Harald Schwalbe
Institut für Organische Chemie und Chemische Biologie
Johann Wolfgang Goethe Universität
Max-von-Laue-Str. 7
D-60438 Frankfurt am Main
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