concanavalin-a and calix(4)arene

The synthesis, characterization and inclusion in liposomes of a glucosylated bolaamphiphile built on a calix[4]arene scaffold are described. The new glucocalixarene bolaamphiphile destabilizes bilayers of saturated lipids whereas it rigidifies those of unsaturated lipids, thus reducing leakage of calcein from the liposome internal aqueous compartment. Moreover, from fluorescence and turbidimetry experiments it was found that the glucose units of bolaamphiphile 1 functionalised liposomes allow a specific multivalent interaction with the tetrameric glucose binding protein Concanavalin A. These results therefore represent a novel strategy to functionalise liposomes with saccharides, exploiting multivalent glycosylated ligands to be used in the preparation of drug delivery systems potentially able to target specific lectins.

Topics: Calixarenes; Concanavalin A; Drug Delivery Systems; Furans; Glucose; Lectins; Lipid Bilayers; Liposomes; Models, Molecular; Molecular Structure; Phenols; Pyridones

The thiourea group has been exploited to link two or four carbohydrate units at the upper rim of tetrapropoxycalix[4]arene derivatives in the cone conformation. Two synthetic methodologies were used, the first one consisting of the condensation of di- and tetraminocalix[4]arenes with the isothiocyanate of monosaccharides in dry CH2Cl2 at room temperature and the second one exploiting the condensation of an aminolactoside with a calixarene isothiocyanate. The first method allows the glycoconjugates to be obtained in 75-80% overall yields. The disfunctionalized derivatives exist in a closed flattened cone conformation in CDCl3 and CD3OD due to the formation of intramolecular hydrogen bonds involving the thiourea groups which are broken in DMSO-d6 to give an open flattened cone conformation. The thiourea groups act not only as linkers but also as binding units for anionic substrates as evidenced by solution 1H NMR and ESI-MS experiments. Turbidimetric analysis indicates that the tetraglucoside and tetragalactoside clusters give specific interactions with Concanavalin A (Con A) and peanut lectin (PNA), respectively. Both features show that the neoglycoconjugates could also be used as site specific molecular delivery systems.

Topics: Calixarenes; Concanavalin A; Glycoconjugates; Hydrogen Bonding; Molecular Conformation; Nephelometry and Turbidimetry; Organophosphorus Compounds; Peanut Agglutinin; Phenols; Spectrometry, Mass, Electrospray Ionization; Substrate Specificity; Thiourea