Meuleman, T. J., Dunlop, J. I., Owsianka, A. M., van de Langemheen, H., Patel, A. H. and Liskamp, R. M.J. (2018) Immobilization by surface conjugation of cyclic peptides for effective mimicry of the HCV-envelope E2 protein as a strategy toward synthetic vaccines. Bioconjugate Chemistry, 29(4), pp. 1091-1101. (doi: 10.1021/acs.bioconjchem.7b00755) (PMID:29382188)
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Abstract
Mimicry of the binding interface of antibody-antigen interactions using peptide-based modulators (i.e. epitope mimics) has promising applications for vaccine design. These epitope mimics can be synthesized in a streamlined and straightforward fashion, thereby allowing for high-throughput analysis. The design of epitope mimics is highly influenced by their spatial configuration and structural conformation. It is widely assumed that for proper mimicry sufficient conformational constraints have to be implemented. This paper describes the synthesis of bromide derivatives functional-ized with a flexible TEG linker equipped with a thiol-moiety that could be used to support cyclic or linear peptides. The cyclic and linear epitope mimics were covalently conjugated via the free thiol-moiety on maleimide-activated plate sur-faces. The resulting covalent, uniform, and oriented coated surface of cyclic or linear epitope mimics were subjected to an ELISA to investigate the effect of peptide cyclization with respect to mimicry of an antigen-antibody interaction of the HCV E2 glycoprotein. To our knowledge, the benefit of cyclized peptides over linear peptides has been clearly demon-strated here for the first time. Cyclic epitope mimics, and not the linear epitope mimics, demonstrated specificity towards their monoclonal antibodies HC84.1 and V3.2, respectively. The described strategy for the construction of epitope mimics shows potential for high-throughput screening of key-binding residues by simply changing the amino-acid sequences within synthetic peptides. In this way, leucine-438 has been identified as a key-binding residue for binding monoclonal antibody V3.2.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Liskamp, Professor Robert and Meuleman, Theodorus and Dunlop, Dr James and Owsianka, Dr Anna and Patel, Professor Arvind and Van De Langemheen, Mr Helmus |
| Authors: | Meuleman, T. J., Dunlop, J. I., Owsianka, A. M., van de Langemheen, H., Patel, A. H., and Liskamp, R. M.J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Science and Engineering > School of Chemistry College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Bioconjugate Chemistry |
| Publisher: | American Chemical Society |
| ISSN: | 1043-1802 |
| ISSN (Online): | 1520-4812 |
| Published Online: | 31 January 2018 |
| Copyright Holders: | Copyright © 2018 American Chemical Society |
| First Published: | First published in Bioconjugate Chemistry 29(4):1091-1101 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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