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

被引：32

作者：

Dietz, Julia ^{[1
]}

Koch, Joachim ^{[2
]}

Kaur, Ajit ^{[3
]}

Raja, Chinnappan ^{[4
]}

Stein, Stefan ^{[1
]}

Grez, Manuel ^{[1
]}

Pustowka, Anette ^{[1
]}

Mensch, Sarah ^{[3
]}

Ferner, Jan ^{[3
]}

Moeller, Lars

Bannert, Norbert

Tampe, Robert ^{[2
]}

Divita, Gilles ^{[5
]}

Mely, Yves ^{[4
]}

Schwalbe, Harald ^{[3
]}

Dietrich, Ursula ^{[1
]}

机构：

[1] Inst Biomed Res, D-60596 Frankfurt, Germany

[2] Univ Frankfurt, Inst Biochem, D-6000 Frankfurt, Germany

[3] Univ Frankfurt, Inst Organ Chem & Chem Biol, Ctr Biomol Magnet Resonance, D-60438 Frankfurt, Germany

[4] Univ Strasbourg 1, Dept Pharmacol & Physicochim, Fac Pharm, Inst Gilbert Laustriat,UMR CNRS 7175, F-67070 Strasbourg, France

[5] CNRS, CRBM, F-75700 Paris, France

来源：

CHEMMEDCHEM | 2008年 / 3卷 / 05期

关键词：

antiviral peptides; HIV-1; NMR spectroscopy; RNA packaging; spot synthesis;

D O I：

10.1002/cmdc.200700194

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 on 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-7 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.

引用

页码：749 / 755

页数：7

共 29 条

[1] NMR structure of stem-loop SL2 of the HIV-1 Ψ RNA packaging signal reveals a novel A-U-A base-triple platform [J].