Trimeric heptad repeat synthetic peptides HR1 and HR2 efficiently inhibit HIV-1 entry
| Autor: | Mzoughi, Olfa, Teixido, Meritxell, Planès, Rémi, Serrero, Manutea, Hamimed, Ibtissem, Zurita, Esther, Moreno, Miguel, Granados, Giovana, Lakhdar-Ghazal, Faouzi, BenMohamed, Lbachir, Giralt, Ernest, Bahraoui, Elmostafa |
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| Přispěvatelé: | CARBILLET, Véronique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Laboratory of Cellular and Molecular Immunology, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), University of Barcelona |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Protein Conformation
alpha-Helical Protein Conformation HIV Infections MESH: Peptide Fragments / pharmacology MESH: Drug Design Membrane Fusion MESH: Membrane Fusion / drug effects MESH: Circular Dichroism [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases inhibitors Research Articles MESH: HIV Envelope Protein gp41 / chemistry [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology Circular Dichroism N36 HIV Envelope Protein gp41 AIDS trimers [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases HIV/AIDS Infection Research Article Biochemistry & Molecular Biology MESH: HIV Infections / drug therapy MESH: HIV-1 / pathogenicity MESH: HIV-1 / drug effects Vaccine Related MESH: HIV Infections / genetics MESH: HIV Envelope Protein gp41 / pharmacology Humans MESH: HIV Infections / virology Amino Acid Sequence Vaccine Related (AIDS) C34 MESH: Protein Conformation alpha-Helical MESH: Humans Prevention alpha-Helical MESH: Amino Acid Sequence / genetics Peptide Fragments Good Health and Well Being Drug Design MESH: Peptide Fragments / chemical synthesis HIV-1 [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Immunization Biochemistry and Cell Biology MESH: Peptide Fragments / chemistry MESH: HIV Envelope Protein gp41 / chemical synthesis |
| Zdroj: | Bioscience Reports Bioscience Reports, 2019, 39 (9), pp.1-15. ⟨10.1042/BSR20192196⟩ Bioscience reports, vol 39, iss 9 |
| ISSN: | 0144-8463 1573-4935 |
| DOI: | 10.1042/BSR20192196 |
| Popis: | International audience; The trimeric heptad repeat domains HR1 and HR2 of the human immunodeficiency virus 1 (HIV-1) gp41 play a key role in HIV-1-entry by membrane fusion. To develop efficient inhibitors against this step, the corresponding trimeric-N36 and C34 peptides were designed and synthesized. Analysis by circular dichroism of monomeric and trimeric N36 and C34 peptides showed their capacities to adopt α-helical structures and to establish physical interactions. At the virological level, while trimeric-C34 conserves the same high anti-fusion activity as monomeric-C34, trimerization of N36-peptide induced a significant increase, reaching 500-times higher in anti-fusion activity, against R5-tropic virus-mediated fusion. This result was associated with increased stability of the N36 trimer peptide with respect to the monomeric form, as demonstrated by the comparative kinetics of their antiviral activities during 6-day incubation in a physiological medium. Collectively, our findings demonstrate that while the trimerization of C34 peptide had no beneficial effect on its stability and antiviral activity, the trimerization of N36 peptide strengthened both stability and antiviral activity. This approach, promotes trimers as new promising HIV-1 inhibitors and point to future development aimed toward innovative peptide fusion inhibitors, microbicides or as immunogens. |
| Databáze: | OpenAIRE |
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