ArticleBiochemistry2012
A novel synthetic bivalent ligand to probe chemokine receptor CXCR4 dimerization and inhibit HIV-1 entry.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Structural mechanisms underlying the modulation of CXCR4 by diverse small-molecule antagonists.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Biological and mutational analyses of CXCR4-antagonist interactions and design of new antagonistic analogs.Bioscience reports · 2023Article
- Leveraging the therapeutic, biological, and self-assembling potential of peptides for the treatment of viral infections.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Discoveries and developments of CXCR4-targeted HIV-1 entry inhibitors.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- High affinity CXCR4 inhibitors generated by linking low affinity peptides.European journal of medicinal chemistry · 2019Article
- Design and evaluation of a CXCR4 targeting peptide 4DV3 as an HIV entry inhibitor and a ligand for targeted drug delivery.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019Article
- Novel Bivalent and D-Peptide Ligands of CXCR4 Mobilize Hematopoietic Progenitor Cells to the Blood in C3H/HeJ Mice.Cell transplantation · 2018Article
- Different contributions of chemokine N-terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3.British journal of pharmacology · 2018Article
- Design, synthesis, and biological characterization of novel PEG-linked dimeric modulators for CXCR4.Bioorganic & medicinal chemistry · 2016Article
- Function-oriented development of CXCR4 antagonists as selective human immunodeficiency virus (HIV)-1 entry inhibitors.Journal of medicinal chemistry · 2015Article
- Stoichiometry and geometry of the CXC chemokine receptor 4 complex with CXC ligand 12: molecular modeling and experimental validation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- A novel CXCR4-selective high-affinity fluorescent probe and its application in competitive binding assays.Biochemistry · 2014Article
- Targeting chemokine receptor CXCR4 for treatment of HIV-1 infection, tumor progression, and metastasis.Current topics in medicinal chemistry · 2014Review
- Bivalent ligands targeting chemokine receptor dimerization: molecular design and functional studies.Current topics in medicinal chemistry · 2014Review
- Multiplex detection of homo- and heterodimerization of g protein-coupled receptors by proximity biotinylation.PloS one · 2014Article
- Molecular recognition of CXCR4 by a dual tropic HIV-1 gp120 V3 loop.Biophysical journal · 2013Article
- A synthetic bivalent ligand of CXCR4 inhibits HIV infection.Biochemical and biophysical research communications · 2013Article
- Non-natural peptide triazole antagonists of HIV-1 envelope gp120.ChemMedChem · 2013Article
- Chemokine receptor oligomerization and allostery.Progress in molecular biology and translational science · 2013Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Chemokine receptor CXCR4 is one of two principal coreceptors for the entry of HIV-1 into target cells. CXCR4 is known to form homodimers. We previously demonstrated that the amino terminus of viral macrophage protein II (vMIP-II) is the major determinant for CXCR4 recognition, and that V1 peptide derived from the N-terminus of vMIP-II (1-21 residues) showed significant CXCR4 binding. Interestingly, an all-d-amino acid analogue of V1 peptide, DV1 peptide, displayed an even higher binding affinity and strong antiviral activity in inhibiting the replication of CXCR4-dependent HIV-1 strains. In this study, we synthetically linked two DV1 peptides with the formation of a disulfide bond between the two cysteine residues present in the peptide sequence to generate a dimeric molecule potentially capable of interacting with two CXCR4 receptors. DV1 dimer exhibited enhanced binding affinity and antiviral activity compared with those of DV1 monomer. Ligand binding site mapping experiments showed that DV1 dimer overlaps with HIV-1 gp120 on CXCR4 binding sites, including several transmembrane (TM) residues located close to the extracellular side and the N-terminus of CXCR4. This finding was supported by the molecular modeling of CXCR4 dimer-DV1 dimer interaction based on the crystal structure of CXCR4, which showed that DV1 dimer is capable of interacting with the CXCR4 dimeric structure by allowing the N-terminus of each DV1 monomer to reach into the binding pocket of CXCR4 monomer. The development of this bivalent ligand provides a tool for further probing the functions of CXCR4 dimerization and studying CXCR4 heterodimerization with other receptors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.