Negatively charged glyconanoparticles modulate and stabilize the secondary structures of a gp120 V3 loop peptide: toward fully synthetic HIV vaccine candidates
| Autor: | Paolo Di Gianvincenzo, Amparo Álvarez, Javier Ezquerra Calvo, Luis M. Bedoya, Soledad Penadés, José Alcamí, Serge Pérez |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Immunogen Immunoconjugates Molecular Sequence Data Static Electricity Biomedical Engineering Pharmaceutical Science Bioengineering Peptide HIV Infections V3 loop HIV Envelope Protein gp120 Antibodies Viral Protein Structure Secondary Protein structure Neutralization Tests Animals Humans Amino Acid Sequence Surface plasmon resonance Peptide sequence Protein secondary structure Pharmacology chemistry.chemical_classification AIDS Vaccines Vaccines Synthetic Chemistry Protein Stability Organic Chemistry Rational design Antibodies Monoclonal Combinatorial chemistry Antibodies Neutralizing Biophysics HIV-1 Nanoparticles Female Gold Rabbits Biotechnology |
| Zdroj: | Bioconjugate chemistry. 26(4) |
| ISSN: | 1520-4812 |
| Popis: | The third variable region (V3 peptide) of the HIV-1 gp120 is a major immunogenic domain of HIV-1. Controlling the formation of the immunologically active conformation is a crucial step to the rational design of fully synthetic candidate vaccines. Herein, we present the modulation and stabilization of either the α-helix or β-strand conformation of the V3 peptide by conjugation to negatively charged gold glyconanoparticles (GNPs). The formation of the secondary structure can be triggered by the variation of the buffer concentration and/or pH as indicated by circular dichoism. The peptide on the GNPs shows increased stability toward peptidase degradation as compared to the free peptide. Moreover, only the V3β-GNPs bind to the anti-V3 human broadly neutralizing mAb 447-52D as demonstrated by surface plasmon resonance (SPR). The strong binding of V3β-GNPs to the 447-52D mAb was the starting point to address its study as immunogen. V3β-GNPs elicit antibodies in rabbits that recognize a recombinant gp120 and the serum displayed low but consistent neutralizing activity. These results open up the way for the design of new fully synthetic HIV vaccine candidates. |
| Databáze: | OpenAIRE |
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