title: Glycodendrimersomes from Sequence-Defined Janus Glycodendrimers Reveal High Activity and Sensor Capacity for the Agglutination by Natural Variants of Human Lectins.
abstract: A library of eight amphiphilic Janus glycodendrimers (Janus-GDs) presenting D-lactose (Lac) and a combination of Lac with up to eight methoxytriethoxy (3EO) units in a sequence-defined arrangement was synthesized via an iterative modular methodology. The length of the linker between Lac and the hydrophobic part of the Janus-GDs was also varied. Self-assembly by injection from THF solution into phosphate-buffered saline led to unilamellar, monodisperse glycodendrimersomes (GDSs) with dimensions predicted by Janus-GD concentration. These GDSs provided a toolbox to measure bioactivity profiles in agglutination assays with sugar-binding proteins (lectins). Three naturally occurring forms of the human adhesion/growth-regulatory lectin galectin-8, Gal-8S and Gal-8L, which differ by the length of linker connecting their two active domains, and a single amino acid mutant (F19Y), were used as probes to study activity and sensor capacity. Unpredictably, the sequence of Lac on the Janus-GDs was demonstrated to determine bioactivity, with the highest level revealed for a Janus-GD with six 3EO groups and one Lac. A further increase in Lac density was invariably accompanied by a substantial decrease in agglutination, whereas a decrease in Lac density resulted in similar or lower bioactivity and sensor capacity. Both changes in topology of Lac presentation of the GDSs and seemingly subtle alterations in protein structure resulted in different levels of bioactivity, demonstrating the presence of regulation on both GDS surface and lectin. These results illustrate the applicability of Janus-GDs to dissect structure-activity relationships between programmable cell surface models and human lectins in a highly sensitive and physiologically relevant manner.
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Sherman
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Muncan
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Andrea D M
authors.initials: AD
authors.lastname: Ramos Vicente
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6391, United States.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6391, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
authors.affiliation: Electron Microscopy Resource Laboratory, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6082, United States.
authors.forename: Dewight
authors.initials: D
authors.lastname: Williams
authors.affiliation: Department of Materials Science & Engineering, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Materials Science & Engineering, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Pochan
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University , Veterinärstrasse 13, 80539 Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Vértesy
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University , Veterinärstrasse 13, 80539 Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.affiliation: Institute of Computational Molecular Science, Temple University , Philadelphia, Pennsylvania 19122, United States.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University , Veterinärstrasse 13, 80539 Munich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Virgil
authors.initials: V
authors.lastname: Percec
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D007785:Lactose / Q000737:chemistry; D037102:Lectins / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission
chemical_list: D050091:Dendrimers; D037102:Lectins; D007785:Lactose