期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 125, 期 28, 页码 8465-8475出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja035636f
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We here report a novel example of artificial glycoviral vectors constructed via number- and size-controlled gene (pCMVluc, 7040 bp) coating with micellar glycocluster nanoparticles (GNPs) of calix[4]-resorcarene-based macrocyclic glycocluster amphiphiles having eight or five saccharide moieties with terminal alpha-glucose (alpha-Glc), beta-glucose (beta-Glc), or beta-galactose (beta-Gal) residues. The resulting glycoviruses are compactly packed (similar to50 nm) and well charge-shielded (zeta congruent to 0 mV), undergo saccharide-dependent (alpha-Glc > beta-Gal much greater than beta-Glc) self-aggregation, and transfect cell (Hela and HepG2) cultures as triggered by the pinocytic form of endocytosis. The semilogarithmic linear size-activity correlation suggests that size-restricted pinocytosis (<100 nm) is effective only for monomeric viruses. The activities of oligomeric and otherwise poorly active beta-Gal-functionalized viruses toward hepatic HepG2 cells are similar to10(2)-times higher than expected on the size basis, owing to the receptor-mediated specific pathway involving the asialoglycoprotein receptors on the hepatic cell surfaces. The scope and prospect of artificial glycoviruses are discussed.
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