Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
December 04, 2014
Very Important Paper: Reconstructing the Discontinuous and Conformational β1/β3-Loop Binding Site on hFSH/hCG by Using Highly Constrained Multicyclic Peptides
Linde E.J. Smeenk, Drohpatie Timmers-Parohi, Joris J. Benschop, Wouter C. Pouijk, Henk Hiemstra, Jan H. van Maarseveen, Peter Timmerman*
Mimicking the binding surface of a protein with peptide-based “small molecules” remains a key challenge in biomedical sciences. In order to achieve maximal binding, different peptide domains involved in binding need to be properly linked and positioned onto a core scaffold molecule. Now, Peter Timmerman (University of Amsterdam) and co-workers describe a novel methodology for producing peptide-based mimics of discontinuous epitopes on hFSHβ and hCGβ. They show the need for multiple constraints for successful mimicry of these complex epitopes. Moreover, tri- and tetracyclic peptides show an over 100-fold improvement in binding, when compared to linear and single-loop peptides. These newly developed mimics may eventually provide novel therapeutics or ultimately be used as synthetic vaccines.
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