Adaptive Synthesis, Supramolecular Behavior, and Biological Properties of Amphiphilic Carbosilane-Phosphonium Dendrons with Tunable Structure.

Here, we present a modular synthesis as well as physicochemical and biological evaluation of a new series of amphiphilic dendrons carrying triphenylphosphonium groups at their periphery. Within the series, the size and mutual balance of lipophilic and hydrophilic domains are systematically varied, changing the dendron shape from cylindrical to conical. In physiological solution, the dendrons exhibit very low critical micelle concentrations (2.

Influence of Selective Deoxyfluorination on the Molecular Structure of Type-2 -Acetyllactosamine.

-Acetyllactosamine is a common saccharide motif found in various biologically active glycans. This motif usually works as a backbone for additional modifications and thus significantly influences glycan conformational behavior and biological activity. In this work, we have investigated the type-2 -acetyllactosamine scaffold using the complete series of its monodeoxyfluorinated analogs.

Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior.

Galectins, the glycan binding proteins, and their respective carbohydrate ligands represent a unique fundamental regulatory network modulating a plethora of biological processes. The advances in galectin-targeted therapy must be based on a deep understanding of the mechanism of ligand-protein recognition. Carbosilane dendrimers, the well-defined and finely tunable nanoscaffolds with low toxicity, are promising for multivalent carbohydrate ligand presentation to target galectin receptors.

Carbosilane Glycodendrimers for Anticancer Drug Delivery: Synthetic Route, Characterization, and Biological Effect of Glycodendrimer-Doxorubicin Complexes.

The complexity of drug delivery mechanisms calls for the development of new transport system designs. Here, we report a robust synthetic procedure toward stable glycodendrimer (glyco-DDM) series bearing glucose, galactose, and oligo(ethylene glycol)-modified galactose peripheral units. In vitro cytotoxicity assays showed exceptional biocompatibility of the glyco-DDMs.

Transport of Anions across the Dialytic Membrane Induced by Complexation toward Dendritic Receptors.

A novel approach to inducing anion transport over the dialytic membrane was proposed and successfully tested using the dihydrogen phosphate anion. The anion receptor based on isophthalamide was anchored on a dendritic skeleton, resulting in a macromolecular structure with a limited possibility to cross the dialytic membrane. The dendritic receptor was placed in a compartment separated from a mother anion solution by a membrane.

Development of α-Selective Glycosylation for the Synthesis of Deoxyfluorinated T Antigen Analogues.

The Tn antigen (GalNAcα1-Thr/Ser) is abundantly expressed in many tumors but rarely found in healthy tissues, which makes it an attractive epitope for antitumor immunotherapy. The use of the Tn antigen in the development of therapeutic antitumor vaccines is hampered by its low immunogenicity, which may be enhanced by deoxyfluorination of the GalNAc moiety. Here, we report the synthesis of protected 3- and 4-fluoro analogues of the threonine-containing Tn antigen.

Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors.

Control of anomeric stereoselectivity in glycosylation with deoxofluorinated glycosyl donors is critical for assembly of fluorinated oligosaccharides. Here, we report the synthesis of benzylated 3-fluoro and 4-fluoro analogues of phenyl 1-thioglucosazide and galactosazide donors and evaluation of their stereoselectivity in glycosylation of a series of model carbohydrate acceptors using the TfO/PhSO promoter system. Low-temperature NMR revealed formation of covalent α-triflate and both anomers of oxosulfonium triflates under selected glycosylation conditions.