An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site
We have previously isolated nucleic acid ligands (aptamers) that bind the surface envelope glycoprotein, gp120, of HIV-1, and neutralize infection of diverse sub-types of virus. Our earlier studies have identified the overall structure of one of these aptamers, B40, and have indicated that it binds...
| Hauptverfasser: | , , , , , , |
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| Format: | Journal article |
| Sprache: | English |
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Elsevier
2008
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| _version_ | 1826307906686943232 |
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| author | Cohen, C James, W Forzan, M Sproat, B Pantophlet, R McGowan, I Burton, D |
| author_facet | Cohen, C James, W Forzan, M Sproat, B Pantophlet, R McGowan, I Burton, D |
| author_sort | Cohen, C |
| collection | OXFORD |
| description | We have previously isolated nucleic acid ligands (aptamers) that bind the surface envelope glycoprotein, gp120, of HIV-1, and neutralize infection of diverse sub-types of virus. Our earlier studies have identified the overall structure of one of these aptamers, B40, and have indicated that it binds to gp120 in a manner that competes with that of the HIV-1 coreceptor, CCR5, and select “CD4i” antibodies with epitopes overlapping this region. Here, we sought to map the B40 binding site on gp120 more precisely by analysing its interaction with a panel of alanine substitution mutants of gp120. Furthermore, we tested our hypothesis concerning the structure of the 40 nucleotide functional core of the aptamer by the solid-phase synthesis of truncated and chemically modified derivatives. The results confirm our structural predictions and demonstrate that aptamer B40 neutralizes a diverse range of HIV-1 isolates as a result of binding to relatively conserved residues on gp120 at the heart of the CCR5-binding site. These structural insights may provide the basis for the development of potential anti-viral agents with high specificity and robustness. |
| first_indexed | 2024-03-07T07:10:03Z |
| format | Journal article |
| id | oxford-uuid:f4c0344e-0293-43ab-a5f7-2b1d1a45403d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:10:03Z |
| publishDate | 2008 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:f4c0344e-0293-43ab-a5f7-2b1d1a45403d2022-06-13T09:19:04ZAn aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding siteJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f4c0344e-0293-43ab-a5f7-2b1d1a45403dEnglishSymplectic Elements at OxfordElsevier2008Cohen, CJames, WForzan, MSproat, BPantophlet, RMcGowan, IBurton, DWe have previously isolated nucleic acid ligands (aptamers) that bind the surface envelope glycoprotein, gp120, of HIV-1, and neutralize infection of diverse sub-types of virus. Our earlier studies have identified the overall structure of one of these aptamers, B40, and have indicated that it binds to gp120 in a manner that competes with that of the HIV-1 coreceptor, CCR5, and select “CD4i” antibodies with epitopes overlapping this region. Here, we sought to map the B40 binding site on gp120 more precisely by analysing its interaction with a panel of alanine substitution mutants of gp120. Furthermore, we tested our hypothesis concerning the structure of the 40 nucleotide functional core of the aptamer by the solid-phase synthesis of truncated and chemically modified derivatives. The results confirm our structural predictions and demonstrate that aptamer B40 neutralizes a diverse range of HIV-1 isolates as a result of binding to relatively conserved residues on gp120 at the heart of the CCR5-binding site. These structural insights may provide the basis for the development of potential anti-viral agents with high specificity and robustness. |
| spellingShingle | Cohen, C James, W Forzan, M Sproat, B Pantophlet, R McGowan, I Burton, D An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site |
| title | An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site |
| title_full | An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site |
| title_fullStr | An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site |
| title_full_unstemmed | An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site |
| title_short | An aptamer that neutralizes R5 strains of HIV-1 binds to core residues of gp120 in the CCR5 binding site |
| title_sort | aptamer that neutralizes r5 strains of hiv 1 binds to core residues of gp120 in the ccr5 binding site |
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