title: Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal Psi.
abstract: 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.
authors.affiliation: Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Str. 42-44, 60596 Frankfurt, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Dietz
authors.forename: Joachim
authors.initials: J
authors.lastname: Koch
authors.forename: Ajit
authors.initials: A
authors.lastname: Kaur
authors.forename: Chinnappan
authors.initials: C
authors.lastname: Raja
authors.forename: Stefan
authors.initials: S
authors.lastname: Stein
authors.forename: Manuel
authors.initials: M
authors.lastname: Grez
authors.forename: Anette
authors.initials: A
authors.lastname: Pustowka
authors.forename: Sarah
authors.initials: S
authors.lastname: Mensch
authors.forename: Jan
authors.initials: J
authors.lastname: Ferner
authors.forename: Lars
authors.initials: L
authors.lastname: Möller
authors.forename: Norbert
authors.initials: N
authors.lastname: Bannert
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
authors.forename: Gilles
authors.initials: G
authors.lastname: Divita
authors.forename: Yves
authors.initials: Y
authors.lastname: Mély
authors.forename: Harald
authors.initials: H
authors.lastname: Schwalbe
authors.forename: Ursula
authors.initials: U
authors.lastname: Dietrich
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D015683:Gene Products, gag / Q000737:chemistry*; D016679:Genome, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry*; D019065:Virus Assembly
chemical_list: D019380:Anti-HIV Agents; D015683:Gene Products, gag; D010455:Peptides; D012367:RNA, Viral