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Xiao Q , Delbianco M , Sherman SE , Reveron Perez AM , Bharate P , Pardo-Vargas A , Rodriguez-Emmenegger C , Kostina NY , Rahimi K , Soder D , Moller M , Klein ML , Seeberger PH , Percec V
Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers
Proc Natl Acad Sci U S A. 2020 jun 2;117(22) :11931-11939
PMID: 32424105 PMCID: PMC7275670 URL: https://www.ncbi.nlm.nih.gov/pubmed/32424105
AbstractCell 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.
Notes1091-6490 Xiao, Qi ORCID: https://orcid.org/0000-0002-6470-0407 Delbianco, Martina ORCID: https://orcid.org/0000-0002-4580-9597 Sherman, Samuel E Reveron Perez, Aracelee M Bharate, Priya Pardo-Vargas, Alonso Rodriguez-Emmenegger, Cesar Kostina, Nina Yu Rahimi, Khosrow Soder, Dominik Moller, Martin Klein, Michael L Seeberger, Peter H ORCID: https://orcid.org/0000-0003-3394-8466 Percec, Virgil Journal Article United States Proc Natl Acad Sci U S A. 2020 May 18. pii: 2003938117. doi: 10.1073/pnas.2003938117.