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

Organic & Biomolecular Chemistry
Paul R WerkhovenRob M J Liskamp

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.

References

Nov 11, 2003·Journal of Combinatorial Chemistry·Cristina Chamorro, Rob M J Liskamp
Apr 7, 2005·Chembiochem : a European Journal of Chemical Biology·Peter TimmermanRob H Meloen
Aug 8, 2006·Chembiochem : a European Journal of Chemical Biology·Yashveer SinghPascal Dumy
Nov 23, 2006·Journal of Receptor and Signal Transduction Research·Raimo FrankeJutta Eichler
Jun 12, 2010·Chemical Communications : Chem Comm·Georg Michael FischerAndreas Zumbusch
Sep 1, 2012·Chemical Communications : Chem Comm·Gwenn E MulderRob M J Liskamp
Dec 21, 2012·Chemical Biology & Drug Design·David J CraikDavid Price
Mar 8, 2013·Organic & Biomolecular Chemistry·Gwenn E MulderRob M J Liskamp
Apr 9, 2014·Organic Letters·Helmus van de LangemheenRob M J Liskamp
May 23, 2014·Organic & Biomolecular Chemistry·Helmus van de LangemheenRob M J Liskamp
Feb 3, 2015·Chembiochem : a European Journal of Chemical Biology·Andrea GroßJutta Eichler

Citations

Dec 17, 2016·Chembiochem : a European Journal of Chemical Biology·Helmus van de LangemheenRob M J Liskamp
Jan 28, 2020·Journal of Peptide Science : an Official Publication of the European Peptide Society·Theodorus J MeulemanRob M J Liskamp

Related Concepts

Alkynes
Antigenic Specificity
Azides
Cyclic Peptides
Structure-Activity Relationship
Semisynthetic Vaccines
HIV Envelope Protein gp120
CD4 Antigens
Immobilized Proteins
Cycloaddition Reaction

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