title: Modular synthesis of amphiphilic Janus glycodendrimers and their self-assembly into glycodendrimersomes and other complex architectures with bioactivity to biomedically relevant lectins.
abstract: The modular synthesis of 7 libraries containing 51 self-assembling amphiphilic Janus dendrimers with the monosaccharides D-mannose and D-galactose and the disaccharide D-lactose in their hydrophilic part is reported. These unprecedented sugar-containing dendrimers are named amphiphilic Janus glycodendrimers. Their self-assembly by simple injection of THF or ethanol solution into water or buffer and by hydration was analyzed by a combination of methods including dynamic light scattering, confocal microscopy, cryogenic transmission electron microscopy, Fourier transform analysis, and micropipet-aspiration experiments to assess mechanical properties. These libraries revealed a diversity of hard and soft assemblies, including unilamellar spherical, polygonal, and tubular vesicles denoted glycodendrimersomes, aggregates of Janus glycodendrimers and rodlike micelles named glycodendrimer aggregates and glycodendrimermicelles, cubosomes denoted glycodendrimercubosomes, and solid lamellae. These assemblies are stable over time in water and in buffer, exhibit narrow molecular-weight distribution, and display dimensions that are programmable by the concentration of the solution from which they are injected. This study elaborated the molecular principles leading to single-type soft glycodendrimersomes assembled from amphiphilic Janus glycodendrimers. The multivalency of glycodendrimersomes with different sizes and their ligand bioactivity were demonstrated by selective agglutination with a diversity of sugar-binding protein receptors such as the plant lectins concanavalin A and the highly toxic mistletoe Viscum album L. agglutinin, the bacterial lectin PA-IL from Pseudomonas aeruginosa, and, of special biomedical relevance, human adhesion/growth-regulatory galectin-3 and galectin-4. These results demonstrated the candidacy of glycodendrimersomes as new mimics of biological membranes with programmable glycan ligand presentations, as supramolecular lectin blockers, vaccines, and targeted delivery devices.
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA. Percec@sas.upenn.edu
authors.forename: Virgil
authors.initials: V
authors.lastname: Percec
authors.forename: Pawaret
authors.initials: P
authors.lastname: Leowanawat
authors.forename: Hao-Jan
authors.initials: HJ
authors.lastname: Sun
authors.forename: Oleg
authors.initials: O
authors.lastname: Kulikov
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Nusbaum
authors.forename: Tam M
authors.initials: TM
authors.lastname: Tran
authors.forename: Annabelle
authors.initials: A
authors.lastname: Bertin
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Wilson
authors.forename: Mihai
authors.initials: M
authors.lastname: Peterca
authors.forename: Shaodong
authors.initials: S
authors.lastname: Zhang
authors.forename: Neha P
authors.initials: NP
authors.lastname: Kamat
authors.forename: Kevin
authors.initials: K
authors.lastname: Vargo
authors.forename: Diana
authors.initials: D
authors.lastname: Moock
authors.forename: Eric D
authors.initials: ED
authors.lastname: Johnston
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Pochan
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Chen
authors.forename: Yoann M
authors.initials: YM
authors.lastname: Chabre
authors.forename: Tze C
authors.initials: TC
authors.lastname: Shiao
authors.forename: Milan
authors.initials: M
authors.lastname: Bergeron-Brlek
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: René
authors.initials: R
authors.lastname: Roy
authors.forename: Hans-J
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heiney
mesh_terms: D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D005690:Galactose / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007785:Lactose / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D008358:Mannose / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D001386:Azides; D050091:Dendrimers; D037102:Lectins; D054852:Small Molecule Libraries; D013501:Surface-Active Agents; D007785:Lactose; D008358:Mannose; D005690:Galactose