Supramolecular Glycodendrimer-Based Hybrid Drugs

Abstract

Specific noncovalent interactions are commonly used by nature to modulate numerous processes including cell recognition, viral adhesion, and transmembrane communications. Here we report on the design, synthesis, and preliminary characterization of new supramolecular glycodendrimer-based hybrid drugs based on adamantyl-modified glycodendrimers of third, fourth, or fifth generation (mPPI-G3-AdaB, mPPI-G4-AdaB, and mPPI-G5-AdaB) and a new heterobifunctional ligand. This component was tailored to bind through noncovalent interactions both the multimeric natural 5-HT3 receptor (through an optimized arylpiperazine pharmacophore) and the adamantyl groups located on the glycodendrimer surfaces (through a β-cyclodextrin residue) giving rise to biorelevant supramolecular constructs.

Multivalent ligands for the serotonin 5-HT4 receptor

“…Consistent with our research on development of 5-HT receptor ligands, [11][12][13][14][15][16][17] we evaluated a series of new multivalent 5-HT 4 R ligands. Following the guidance of Berque-Bestel et al, 8,9 we used the same protomeric unit (i.e., 2, tethered at the 4-position of the piperidine moiety) as an active entity, because a partial agonist would facilitate detection of a potential increase of efficacy.…”

Immobilization of multivalent glycoprobes on gold surfaces for sensing proteins and macrophages

“…In addition to an increase in avidity, multivalency enhances the selectivity of a particular interaction and amplifies small differences in the intrinsic binding avidity. 4,5 Recently, an attempt has been initiated to synthesize multivalent probes using peptides, 6 polymers, 7 dendrimers, 8,9 nanoparticles and supramolecular complexes, 10 for studying the carbohydrate-protein interactions in solution based techniques. [11][12][13] Alternatively, surface immobilization of monovalent sugars presents multivalent arrays to facilitate the analysis of lectin binding and can be relevant to the cell surface carbohydrate presentation.…”

Mono-6-Substituted Cyclodextrins—Synthesis and Applications

“…The yield was 67%; the interaction of the product with adamantane containing thermoresponsive copolymer was studied. Paolino et al [ 169 ] used microwave irradiation and a mixture of 0.5 eq. of CuBr and a 0.5 eq.…”