Mechanism of anti-HIV activity of negatively charged albumins: Biomolecular interaction with the HIV-1 envelope protein gp120
| Autor: | M.E. Kuipers, J.G Huisman, MP de Béthune, E. De Clercq, R Pauwels, Pieter Swart, Dkf Meijer, Hanneke Schuitemaker |
|---|---|
| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
polyanionic proteins
Immunology Molecular Sequence Data Mannose Plasma protein binding V3 loop HIV Envelope Protein gp120 PHENOTYPE Binding Competitive SULFATED POLYSACCHARIDES chemistry.chemical_compound PRINCIPAL NEUTRALIZING DOMAIN DEXTRAN SULFATE Virology Albumins binding affinity SYNTHETIC PEPTIDES Immunology and Allergy Humans Amino Acid Sequence Peptide sequence Serum Albumin chemistry.chemical_classification Oligopeptide GLUCOSAMINYL-BINDING-PROPERTIES HUMAN SERUM ALBUMINS V3 Chemistry Sepharose Albumin GLYCOPROTEIN Hydrogen-Ion Concentration IMMUNODEFICIENCY-VIRUS TYPE-1 Microspheres Peptide Fragments negatively charged albumins Amino acid Dissociation constant gp120 Biochemistry Carbohydrate Sequence HIV-1 Protein Binding |
| Zdroj: | Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 11(5), 419-429 Journal of acquired immune deficiency syndromes and human retrovirology, 11(5), 419-429. Lippincott Williams and Wilkins |
| ISSN: | 1077-9450 |
| Popis: | A novel class of polyanionic proteins with potent anti-human immunodeficiency virus type 1 activity, the negatively charged albumins (NCAs), have been reported previously. In vitro antiviral assays established that these compounds preferentially inhibit virus-cell fusion and syncytium formation and that virus-cell binding is less affected. Here the interaction of the NCAs with synthetic peptides composed of 15-36 amino acids and corresponding to different parts of the gp120 envelope protein is described. Among the gp120 peptides tested, binding of the NCAs was observed only with the so-called V3 loop (amino acids 296-330) and the C-terminal part of gp120. A higher number of negatively charged residues in the albumins resulted in higher binding affinities. NCAs in which, in addition to negative charges, up to 7 or 14 lactose or mannose groups were introduced, respectively, did not exhibit increasing binding affinity. In contrast, mannosylated albumin containing about 14 mannose groups showed an increased binding compared with native albumin. Binding of the NCAs to the V3 and C-terminal oligopeptide was competitively inhibited by sulfated polysaccharide heparin and dextran sulfate. This finding indicates that the binding between the gp120 peptides and the NCAs is likely caused by electrostatic interactions. However, the fact that the dissociation constants of dextran sulfate and heparin are orders of magnitude larger compared with the NCAs indicates that the spatial structure of the proteins and/or hydrophobic interactions between the NCAs and the envelope protein may also be involved. |
| Databáze: | OpenAIRE |
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