Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold

Werkhoven, P.R., Elwakiel, M., Meuleman, T.J., Quarles van Ufford, H.C., Kruijtzer, J.A.W. and Liskamp, R.M.J. (2016) Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold. Organic and Biomolecular Chemistry, 14(2), pp. 701-710. (doi: 10.1039/c5ob02014j) (PMID:26552661)

Abstract

Mimics of discontinuous epitopes of for example bacterial or viral proteins may have considerable potential for the development of synthetic vaccines, especially if conserved epitopes can be mimicked. However, due to the structural complexity and size of discontinuous epitopes molecular construction of these mimics remains challeging. We present here a convergent route for the assembly of discontinuous epitope mimics by successive azide alkyne cycloaddition on an orthogonal alkyne functionalized scaffold. Here the synthesis of mimics of the HIV gp120 discontinuous epitope that interacts with the CD4 receptor is described. The resulting protein mimics are capable of inhibition of the gp120–CD4 interaction. The route is convergent, robust and should be applicable to other discontinuous epitopes.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert
• Authors: Werkhoven, P.R., Elwakiel, M., Meuleman, T.J., Quarles van Ufford, H.C., Kruijtzer, J.A.W., and Liskamp, R.M.J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Organic and Biomolecular Chemistry
• Publisher: Royal Society of Chemistry
• ISSN: 1477-0520
• ISSN (Online): 1477-0539
• Published Online: 05 November 2015
• Copyright Holders: Copyright © 2016 The Royal Society of Chemistry
• First Published: First published in Organic and Biomolecular Chemistry 14:701-710
• Publisher Policy: Reproduced under a creative commons license