Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers.
Biomimetics
/ methods
Cell Membrane
/ chemistry
Dendrimers
/ chemical synthesis
Glycoconjugates
/ chemical synthesis
Glycolipids
/ chemistry
Hydrophobic and Hydrophilic Interactions
Isothiocyanates
/ metabolism
Lectins
/ metabolism
Mannose
/ metabolism
Nanoparticles
/ chemistry
Oligosaccharides
/ metabolism
Polysaccharides
/ metabolism
Translational Research, Biomedical
/ methods
automated glycan assembly
cell membrane mimics
isothiocyanate–amine coupling
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
02 06 2020
02 06 2020
Historique:
pubmed:
20
5
2020
medline:
18
8
2020
entrez:
20
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32424105
pii: 2003938117
doi: 10.1073/pnas.2003938117
pmc: PMC7275670
doi:
Substances chimiques
Dendrimers
0
Glycoconjugates
0
Glycolipids
0
Isothiocyanates
0
Lectins
0
Oligosaccharides
0
Polysaccharides
0
Mannose
PHA4727WTP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
11931-11939Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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