Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers

Proceedings of the National Academy of Sciences, vol. 117, pp. 11931–11939

Abstract

Cell surfaces are often decorated with glycoconjugates that contain linear and more complex symmetrically and asymmetrically branched carbohydrates essential for cellular recognition and communication processes. Mannose is one of the fundamental building blocks of glycans in many biological membranes. Moreover, oligomannoses are commonly found on the surface of pathogens such as bacteria and viruses as both glycolipids and glycoproteins. However, their mechanism of action is not well understood, even though this is of great potential interest for translational medicine. Sequence-defined amphiphilic Janus glycodendrimers containing simple mono- and disaccharides that mimic glycolipids are known to self-assemble into glycodendrimersomes, which in turn resemble the surface of a cell by encoding carbohydrate activity via supramolecular multivalency. The synthetic challenge of preparing Janus glycodendrimers containing more complex linear and branched glycans has so far prevented access to more realistic cell mimics. However, the present work reports the use of an isothiocyanate-amine "click"-like reaction between isothiocyanate-containing sequence-defined amphiphilic Janus dendrimers and either linear or branched oligosaccharides containing up to six monosaccharide units attached to a hydrophobic amino-pentyl linker, a construct not expected to assemble into glycodendrimersomes. Unexpectedly, these oligoMan-containing dendrimers, which have their hydrophobic linker connected via a thiourea group to the amphiphilic part of Janus glycodendrimers, self-organize into nanoscale glycodendrimersomes. Specifically, the mannose-binding lectins that best agglutinate glycodendrimersomes are those displaying hexamannose. Lamellar "raft-like" nanomorphologies on the surface of glycodendrimersomes, self-organized from these sequence-defined glycans, endow these membrane mimics with high biological activity.

Authors 13

1. Qi Xiao

   University of Pennsylvania · Temple University

   Affiliation as printed

   Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122;

   Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104;

2. Martina Delbianco

   Max Planck Institute of Colloids and Interfaces

   Affiliation as printed

   Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany;

3. Samuel E. Sherman

   University of Pennsylvania

   Affiliation as printed

   Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104;

4. Aracelee M. Reveron Perez

   University of Pennsylvania

   Affiliation as printed

   Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104;

5. Priya Bharate

   Max Planck Institute of Colloids and Interfaces

   Affiliation as printed

   Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany;

6. César Rodriguez‐Emmenegger Aachen DWI - Leibniz Institute for Interactive Materials Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials, 52074 Aachen, Germany;

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany;

7. Nina Yu. Kostina Aachen DWI - Leibniz Institute for Interactive Materials Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials, 52074 Aachen, Germany;

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany;

8. Khosrow Rahimi Aachen DWI - Leibniz Institute for Interactive Materials Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials, 52074 Aachen, Germany;

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany;

9. Dominik Söder Aachen DWI - Leibniz Institute for Interactive Materials Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials, 52074 Aachen, Germany;

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany;

10. Martin Möller Aachen DWI - Leibniz Institute for Interactive Materials Institute of Technical and Macromolecular Chemistry

    DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

    Affiliation as printed

    DWI – Leibniz Institute for Interactive Materials, 52074 Aachen, Germany;

    Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany;

11. Michael Lawrence Klein

    Temple University

    Affiliation as printed

    Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122;

12. Peter H. Seeberger

    Max Planck Institute of Colloids and Interfaces · Freie Universität Berlin

    Affiliation as printed

    Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany;

    Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany

13. Virgil Percec

    University of Pennsylvania

    Affiliation as printed

    Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104;