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Inhibition of HIV‐1 by a Peptide Ligand of the Genomic RNA Packaging Signal Ψ
Author(s) -
Dietz Julia,
Koch Joachim,
Kaur Ajit,
Raja Chinnappan,
Stein Stefan,
Grez Manuel,
Pustowka Anette,
Mensch Sarah,
Ferner Jan,
Möller Lars,
Bannert Norbert,
Tampé Robert,
Divita Gilles,
Mély Yves,
Schwalbe Harald,
Dietrich Ursula
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700194
Subject(s) - rna , capsid , peptide , virus , group specific antigen , chemistry , biology , virology , peptide library , genome , microbiology and biotechnology , computational biology , biochemistry , gene , peptide sequence
The interaction of the nucleocapsid NCp7 of the human immunodeficiency virus type 1 (HIV‐1) Gag polyprotein with the RNA packaging signal Ψ 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 Ψ‐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 Ψ‐RNA binding. The optimized peptide, psi‐pepB , was characterized in detail with respect to its conformation and binding properties for the SL3 of the Ψ 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.