ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Phage display-directed discovery of LEDGF/p75 binding cyclic peptide inhibitors of HIV replication.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Targeting Human Immunodeficiency Virus Integrase Beyond the Active Site: The Discovery and Development of Allosteric Integrase Inhibitors.ChemMedChem · 2026Review
- Phage Display as a Medium for Target Therapy Based Drug Discovery, Review and Update.Molecular biotechnology · 2025Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- CyclicPepedia: a knowledge base of natural and synthetic cyclic peptides.Briefings in bioinformatics · 2024Article
- Design of Vif-Derived Peptide Inhibitors with Anti-HIV-1 Activity by Interrupting Vif-CBFβ Interaction.Viruses · 2024Article
- Propagation Capacity of Phage Display Peptide Libraries Is Affected by the Length and Conformation of Displayed Peptide.Molecules (Basel, Switzerland) · 2023Article
- High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.Metabolites · 2023Review
- Facile de Novo Sequencing of Tetrazine-Cyclized Peptides through UV-Induced Ring-Opening and Cleavage from the Solid Phase.Chembiochem : a European journal of chemical biology · 2023Article
- The cyclic peptide G4CP2 enables the modulation of galactose metabolism in yeast by interfering with GAL4 transcriptional activity.Frontiers in molecular biosciences · 2023Article
- Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins.Journal of hematology & oncology · 2021Review
- Modulating Protein-Protein Interactions by Cyclic and Macrocyclic Peptides. Prominent Strategies and Examples.Molecules (Basel, Switzerland) · 2021Review
- The selenium-containing drug ebselen potently disrupts LEDGF/p75-HIV-1 integrase interaction by targeting LEDGF/p75.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Development of a Cell-Permeable Cyclic Peptidyl Inhibitor against the Keap1-Nrf2 Interaction.The Journal of organic chemistry · 2020Article
- A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library.Angewandte Chemie (International ed. in English) · 2019Review
- Intracellular immunization against HIV infection with an intracellular antibody that mimics HIV integrase binding to the cellular LEDGF protein.Scientific reports · 2017Article
- Targeting intracellular protein-protein interactions with cell-permeable cyclic peptides.Current opinion in chemical biology · 2017Review
- Generation of a cell-permeable cycloheptapeptidyl inhibitor against the peptidyl-prolyl isomerase Pin1.Organic & biomolecular chemistry · 2017Article
- Macrocycles as protein-protein interaction inhibitors.The Biochemical journal · 2017Review
- Different Pathways Leading to Integrase Inhibitors Resistance.Frontiers in microbiology · 2016Review
- Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif.Nature communications · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The interaction between the human immunodeficiency virus (HIV) integrase (IN) and its cellular cofactor lens epithelium-derived growth factor (LEDGF/p75) is crucial for HIV replication. While recently discovered LEDGINs inhibit HIV-1 replication by occupying the LEDGF/p75 pocket in IN, it remained to be demonstrated whether LEDGF/p75 by itself can be targeted. By phage display we identified cyclic peptides (CPs) as the first LEDGF/p75 ligands that inhibit the LEDGF/p75-IN interaction. The CPs inhibit HIV replication in different cell lines without overt toxicity. In accord with the role of LEDGF/p75 in HIV integration and its inhibition by LEDGINs, CP64, and CP65 block HIV replication primarily by inhibiting the integration step. The CPs retained activity against HIV strains resistant to raltegravir or LEDGINs. Saturation transfer difference (STD) NMR showed residues in CP64 that strongly interact with LEDGF/p75 but not with HIV IN. Mutational analysis identified tryptophan as an important residue responsible for the activity of the peptides. Serial passaging of virus in the presence of CPs did not yield resistant strains. Our work provides proof-of-concept for direct targeting of LEDGF/p75 as novel therapeutic strategy and the CPs thereby serve as scaffold for future development of new HIV therapeutics.
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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.