Synthesis of dodecavalent fullerene-based glycoclusters and evaluation of their binding properties towards a bacterial lectin

Multivalency is playing a major role in biological processes and particularly in lectin-carbohydrate interactions. The design of high-affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide-alkyne "click" chemistry was applied to the synthesis of dodecavalent fullerene-based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis-fullerene adduct or glycoside). PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant "glycoside cluster effect" with up to a 12,000-fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene-based glycocluster, albeit with some differences depending on the analytical technique.     

Anchoring Supramolecular Polymers to Human Red Blood Cells by Combining Dynamic Covalent and Non-Covalent Chemistries

Understanding cell/material interactions is essential to design functional cell-responsive materials. While the scientific literature abounds with formulations of biomimetic materials, only a fraction of them focused on mechanisms of the molecular interactions between cells and material. To provide new knowledge on the strategies for materials/cell recognition and binding, supramolecular benzene-1,3,5-tricarboxamide copolymers bearing benzoxaborole moieties are anchored on the surface of human erythrocytes via benzoxaborole/sialic-acid binding. This interaction based on both dynamic covalent and non-covalent chemistries is visualized in real time by means of total internal reflection fluorescence microscopy. Exploiting this imaging method, we observe that the functional copolymers specifically interact with the cell surface. An optimal fiber affinity towards the cells as a function of benzoxaborole concentration demonstrates the crucial role of multivalency in these cell/material interactions.     

Chemoenzymatic Synthesis of a Multivalent Aminoglycoside

A polymeric aminoglycoside was prepared by a facile chemoenzymatic reaction. Boc‐protected aminoglycoside, amikacin, was chemoselectively esterified with divinyl sebacate at a hydroxyl group in the C6″ position by protease from Bacillus subtilis. The resulting 3,6′,3″,4?‐tetra‐N‐Boc‐6″‐O‐vinyl sebacate was copolymerized with maltitol 6‐vinyl sebacate to yield a polymeric amikacin. The polymeric amikacin showed a modest inhibitory effect on in vitro protein synthesis, and a little antibiotic activity in minimum inhibitory concentration (MIC) assay in the presence of protease.

The synthesis of Boc‐protected amikacin ester by an enzyme‐catalyzed (protease) esterification.     

Solid-phase construction: high efficiency dendrimer synthesis using AB3 isocyanate-type monomers

Solid-phase synthesis is an ideal tool for reactions that require high concentrations and excess reagents and forcing chemical conditions. One such chemistry is that required for dendrimer construction. In this paper the synthesis of a series of symmetrical AB₃ isocyanate-type monomers is reported and used for the preparation of tri-branched dendrimers on the solid-phase. This method not only allows isolable dendrimer but can generate high-loading supports and devices for multivalent presentation.