Synthesis of Gold Glyconanoparticles and Biological Evaluation of Recombinant Gp120 Interactions
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文摘
As part of our continuing efforts to study the molecular events involved in HIV recognition of mucosalmembrane cells, we are studying the interactions of the HIV-associated glycoprotein gp120, with thecellular receptor GalCer. In this work, we report investigations of multivalent interactions of Auglyconanoparticles containing galactosyl and glucosyl headgroups with recombinant gp120. These particleswere prepared from disulfides containing C-glycosides linked to triethylene glycol via an amide bond usinga modification of the Brust method.1 Results from transmission electron microscopy, atomic force microscopy,and UV-vis absorption spectroscopy data are consistent with an average particle diameter of 2 nm. Elementalanalyses indicate that the average composition of the particles is 1.6:1 Au:carbohydrate. A biotin-NeutrAvidin adhesion assay was used to evaluate the relative ability of carbohydrate disulfides and Auglyconanopraticles to displace rgp120 from plate-bound GalCer. The data indicate that divalent disulfideswere less than 12% as active as biotinylated GalCer, a water-soluble surrogate of GalCer. However, whenthese same carbohydrates were presented in a polyvalent display on gold, they were greater than 300 timesmore active than the disulfides and at least 20 times more active than biotinylated GalCer. These resultscollectively demonstrate the potential utility of polyvalent ligand arrays on nanoplatforms.

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