A Functionally Selective Synthetic Mimic of the HIV‐1 Co‐receptor CXCR4

Möbius, Kalle; Dürr, Ralf; Haußner, Christina; Dietrich, Ursula; Eichler, Jutta

doi:10.1002/chem.201200111

Cited by 23 publications

(36 citation statements)

References 25 publications

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“…ECL2 of CXCR4 and the N-terminus of CCR5 are indeed major gp120 binding determinants at the coreceptor surface and we have recently shown that peptides derived from ECL2-X4 (176-202) have antiviral properties against X4-strain NL4.3 (IC 50 ¼ 9.3 AE 0.3 mmol/l) (Fig. 1b) [30][31][32][33][34][35][36][37]. These results are consistent with reporting of CCR5 surface mimicry by gp120 specific antibodies CDRs [38,39].…”

mentioning

confidence: 99%

Isolation of an HIV-1 neutralizing peptide mimicking the CXCR4 and CCR5 surface from the heavy-chain complementary determining region 3 repertoire of a viremic controller

Chevigné

Delhalle

Counson

et al. 2016

AIDS

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mentioning

confidence: 99%

Isolation of an HIV-1 neutralizing peptide mimicking the CXCR4 and CCR5 surface from the heavy-chain complementary determining region 3 repertoire of a viremic controller

Chevigné

Delhalle

Counson

et al. 2016

AIDS

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“…We could select an entry inhibitory peptide (XD3) with remarkable homology to the N-terminus of CCR5 and CXCR4 by phage display using CD4i epitopes on native dualtropic Env as target [77]. For CXCR4, which is less dependent on its N-terminus for HIV entry, we further designed a peptide comprising ECL1 to 3 linked to short spacers, which showed selective CXCR4 binding and entry inhibition in the low micromolar range [78].…”

Section: Hiv-1 Coreceptors Ccr5 and Cxcr4 And Inhibitors Of Coreceptomentioning

confidence: 99%

Targeting Cellular Cofactors in HIV Therapy

Dürr

Keppler

Christ

et al. 2014

Topics in Medicinal Chemistry

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Besides viral proteins cellular factors play a key role in the replication of the human immunodeficiency virus HIV-1. The outcome of virus replication is determined by the balance between the activity of a number of cellular dependency factors and restriction factors. Whereas the first are essential cofactors for diverse steps in the viral replication cycle, the latter counteract virus replication by sensing particular viral components as non-self, often as mediators of the innate immune system. Cellular cofactors include receptors for HIV-1 entry, LEDGF as cofactor for the viral integrase, the RNA helicase DDX3 involved in the nuclear export of unspliced viral RNAs, and diverse cellular kinases that promote viral replication. Cellular restriction factors are often antagonized by HIV-1 accessory proteins in order to counteract their restrictive function on viral replication. Although cellular cofactors in the HIV field are understood as factors promoting viral replication, we add a subchapter on the most important restriction factors (Trim5α, APOBEC3G, SAMHD1, and tetherin/BST-2). Today highly active antiretroviral therapy (HAART) mostly targets HIV proteins like reverse transcriptase, protease, or integrase to specifically interfere with virus replication. However, the identification of cellular cofactors and the increasing knowledge on their mode of action at R. Dürr and U. Dietrich (*) Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Str. 42-44, 60596 Frankfurt, Germany e-mail: duerr@gsh.uni-frankfurt.de; ursula.dietrich@gsh.uni-frankfurt.de O. Keppler Institute of Medical Virology, Goethe University, Frankfurt, Germany e-mail: oliver.keppler@kgu.de F. Christ Laboratory for Molecular Virology and Gene Therapy, K.U. Leuven, Leuven, Belgium e-mail: frauke.christ@med.kuleuven.be E. Crespan, A. Garbelli, and G. Maga Institute of Molecular Genetics, IGM-CNR, Pavia, Italy e-mail: emmanuelecrespan@gmail.com; agarbelli@gmail.com; maga@igm.cnr.it defined steps in the HIV-1 replication cycle have opened new avenues towards the development of HIV-1 inhibitors. Here we summarize the most important cellular factors involved in HIV-1 replication along with therapeutic approaches developed to target them, preferentially without harming their normal cellular function.

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“…Peptides were synthesized using Fmoc/t-Bu based solid phase peptide synthesis as previously described for CX4-M1 13,14 . Briefly, peptides were generated as C-terminal amides, and the N-terminus was acetylated.…”

Section: Peptide Synthesismentioning

confidence: 99%

“…This peptide, which presents the three ECLs of CXCR4, was found to selectively bind to HIV-1 gp120 from X4 tropic virus strains 13 , as well as to peptides presenting the V3-loop of these gp120 proteins 14 , which is part of the corecetor binding site of gp120 15 . Furthermore, CX4-M1 selectively inhibits infection of cells with X4-tropic HIV-1 13 . We now asked the question whether this functional selectivity of CX4-M1 is also present in its interaction with the natural ligand of CXCR4, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, peptides that mimic protein binding sites can be used as protein surrogates in binding experiments 11,12 . Recently, we have introduced a CXCR4 mimetic peptide, termed CX4-M1 13 . This peptide, which presents the three ECLs of CXCR4, was found to selectively bind to HIV-1 gp120 from X4 tropic virus strains 13 , as well as to peptides presenting the V3-loop of these gp120 proteins 14 , which is part of the corecetor binding site of gp120 15 .…”

Section: Introductionmentioning

confidence: 99%

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