Gallego Gómez, IvánRamos Soriano, JavierMéndez Ardoy, AlejandroCabrera González, JustoLostalé Seijo, IreneIllescas, BeatrizReina Martín, José JuanMartín León, NazarioMontenegro García, Javier2022-09-262022-09-262022Angew. Chem.Int. Ed.2022,e202210043. https://doi.org/10.1002/anie.2022100431433-7851http://hdl.handle.net/10347/29251Multivalent ligand presentation is a powerful strategy for the development of specific binders and inhibitors. Peptide/[60]fullerene hybrids have now been synthesized that exploit the complete substitution of the fullerene scaffold to afford globular structures presenting twelve copies of a peptide ligand for the recognition of E-selectin. Fully substituted peptide/[60]fullerene hexakis-adducts offer an excellent opportunity for multivalent protein recognition. In contrast to monofunctionalized fullerene hybrids, peptide/[60]fullerene hexakis-adducts display multiple copies of a peptide in close spatial proximity and in the three dimensions of space. High affinity peptide binders for almost any target can be currently identified by in vitro evolution techniques, often providing synthetically simpler alternatives to natural ligands. However, despite the potential of peptide/[60]fullerene hexakis-adducts, these promising conjugates have not been reported to date. Here we present a synthetic strategy for the construction of 3D multivalent hybrids that are able to bind with high affinity the E-selectin. The here synthesized fully substituted peptide/[60]fullerene hybrids and their multivalent recognition of natural receptors constitute a proof of principle for their future application as functional biocompatible materialseng© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposesAtribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/FullerenesGlycomimeticLectinMultivalencyPeptidesjournal article10.1002/anie.2022100431521-3773open access