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Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges
In this research we describe the improvement of the water‐solubility of cyclic epitope mimics based on the HCV E2 glycoprotein by incorporation of suitable polar hinges. The poor solubility of epitope mimics based on peptide sequences in the envelope (E2) protein hampered their synthesis and purific...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050536/ https://www.ncbi.nlm.nih.gov/pubmed/31984607 http://dx.doi.org/10.1002/psc.3222 |
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author | Meuleman, Theodorus J. Cowton, Vanessa M. Patel, Arvind H. Liskamp, Rob M.J. |
author_facet | Meuleman, Theodorus J. Cowton, Vanessa M. Patel, Arvind H. Liskamp, Rob M.J. |
author_sort | Meuleman, Theodorus J. |
collection | PubMed |
description | In this research we describe the improvement of the water‐solubility of cyclic epitope mimics based on the HCV E2 glycoprotein by incorporation of suitable polar hinges. The poor solubility of epitope mimics based on peptide sequences in the envelope (E2) protein hampered their synthesis and purification and made it very difficult to prepare the molecular constructs for evaluation of their bioactivity. Since changes in the amino acid composition are hardly possible in these epitope mimics in order to increase water‐solubility, a polar cyclization hinge may offer a remedy leading to a significant increase of polarity and therefore water solubility. These polar hinges were applied in the synthesis of better water‐soluble HCV‐E2 epitopes. An azide functionality in the polar hinges allowed attachment of a tetraethylene glycol linker by Cu‐catalyzed azide‐alkyne cyclo‐addition (CuAAC) for a convenient conjugation to ELISA plates in order to evaluate the bio‐activity of the epitope mimics. The immunoassays showed that the use of more polar cyclization hinges still supported anti‐HCV antibody recognition and did not negatively influence their binding. This significantly increased solubility induced by polar hinges should therefore allow for the molecular construction and ultimate evaluation of synthetic vaccine molecules. |
format | Online Article Text |
id | pubmed-7050536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70505362020-03-09 Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges Meuleman, Theodorus J. Cowton, Vanessa M. Patel, Arvind H. Liskamp, Rob M.J. J Pept Sci Research Articles In this research we describe the improvement of the water‐solubility of cyclic epitope mimics based on the HCV E2 glycoprotein by incorporation of suitable polar hinges. The poor solubility of epitope mimics based on peptide sequences in the envelope (E2) protein hampered their synthesis and purification and made it very difficult to prepare the molecular constructs for evaluation of their bioactivity. Since changes in the amino acid composition are hardly possible in these epitope mimics in order to increase water‐solubility, a polar cyclization hinge may offer a remedy leading to a significant increase of polarity and therefore water solubility. These polar hinges were applied in the synthesis of better water‐soluble HCV‐E2 epitopes. An azide functionality in the polar hinges allowed attachment of a tetraethylene glycol linker by Cu‐catalyzed azide‐alkyne cyclo‐addition (CuAAC) for a convenient conjugation to ELISA plates in order to evaluate the bio‐activity of the epitope mimics. The immunoassays showed that the use of more polar cyclization hinges still supported anti‐HCV antibody recognition and did not negatively influence their binding. This significantly increased solubility induced by polar hinges should therefore allow for the molecular construction and ultimate evaluation of synthetic vaccine molecules. John Wiley and Sons Inc. 2020-01-26 2020-01 /pmc/articles/PMC7050536/ /pubmed/31984607 http://dx.doi.org/10.1002/psc.3222 Text en © 2020 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Meuleman, Theodorus J. Cowton, Vanessa M. Patel, Arvind H. Liskamp, Rob M.J. Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges |
title | Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges |
title_full | Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges |
title_fullStr | Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges |
title_full_unstemmed | Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges |
title_short | Improving the aqueous solubility of HCV‐E2 glycoprotein epitope mimics by cyclization using POLAR hinges |
title_sort | improving the aqueous solubility of hcv‐e2 glycoprotein epitope mimics by cyclization using polar hinges |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050536/ https://www.ncbi.nlm.nih.gov/pubmed/31984607 http://dx.doi.org/10.1002/psc.3222 |
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