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Issue 16, 2013
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Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries

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Abstract

A diversity of protein surface discontinuous epitope mimics is now rapidly and efficiently accessible. Despite the important role of proteinprotein interactions involving discontinuous epitopes in a wide range of diseases, mimicry of discontinuous epitopes using peptide-based molecules remains a major challenge. Using copper(I) catalyzed azide–alkyne cycloaddition (CuAAC), we have developed a general and efficient method for the synthesis of collections of discontinuous epitope mimics. Up to three different cyclic peptides, representing discontinuous epitopes in HIV-gp120, were conjugated to a selection of scaffold molecules. Variation of the scaffold molecule, optimization of the ring size of the cyclic peptides and screening of the resulting libraries for successful protein mimics led to an HIV gp120 mimic with an IC50 value of 1.7 μM. The approach described here provides rapid and highly reproducible access to clean, smart libraries of very complex bio-molecular constructs representing protein mimics for use as synthetic vaccines and beyond.

Graphical abstract: Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries

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Publication details

The article was received on 20 Dec 2012, accepted on 21 Feb 2013 and first published on 22 Feb 2013


Article type: Paper
DOI: 10.1039/C3OB27470E
Citation: Org. Biomol. Chem., 2013,11, 2676-2684
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    Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries

    G. E. Mulder, H. (Linda). C. Quarles van Ufford, J. van Ameijde, A. J. Brouwer, J. A. W. Kruijtzer and R. M. J. Liskamp, Org. Biomol. Chem., 2013, 11, 2676
    DOI: 10.1039/C3OB27470E

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