Improving the aqueous solubility of HCV-E2 glycoprotein epitope mimics by cyclization using polar hinges

Meuleman, T. J., Cowton, V. M., Patel, A. H. and Liskamp, R. M.J. (2020) Improving the aqueous solubility of HCV-E2 glycoprotein epitope mimics by cyclization using polar hinges. Journal of Peptide Science, 26(1), e3222. (doi: 10.1002/psc.3222) (PMID:31984607)

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Abstract

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.

Item Type:Articles
Additional Information:This research was funded by the University of Glasgow. Work in AHP’s lab was supported by the Medical Research Council grants MC_UU12014/2.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liskamp, Professor Robert and Cowton, Dr Vanessa and Meuleman, Theodorus and Patel, Professor Arvind
Authors: Meuleman, T. J., Cowton, V. M., Patel, A. H., and Liskamp, R. M.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Science and Engineering > School of Chemistry
College of Science and Engineering > School of Engineering
Journal Name:Journal of Peptide Science
Publisher:Wiley
ISSN:1075-2617
ISSN (Online):1099-1387
Published Online:26 January 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Journal of Peptide Science 26(1):e3222
Publisher Policy:Reproduced under a Creative Commons License

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