The lipophilic CdSe quantum dot (QD) coated with trioctylphosphine oxide (TOPOQD) can be extracted from chloroform into water upon interaction with macrocyclic glycocluster amphiphile 1. The QD-conjugated and highly fluorescent sugar ball of a size of 15 nm (TOPOQD1) thus solubilized in water readily invades Hela cells via endocytosis. The endocytic activity of TOPOQD1 (15 nm), in light of those of the micellar homoaggregate of 1 (5 nm) and the virus-like 1-DNA conjugate (50 nm) as references, reveals a dramatic size effect (50 > 15 > 5) in the subviral size region. The optimal size at approximately 50 nm indicates that size complementarity which governs molecular recognition in small host-guest systems also plays key roles in the encapsulation of nanometric guest particles by the endocytic vesicles (=100 nm) as a macrobiomolecular host. The work thus suggests an utmost importance of size control at the viral size when designing molecular (gene, drug, probe, etc.) delivery machines.
An achiral anthracene−pyrimidine derivative (5-(9-anthracenyl)pyrimidine, 1) forms adduct 1·Cd(NO3)2·H2O·EtOH (2) in chiral space group P21. The metal ion is hexacoordinated with two pyrimidine ligands
(equatorial cis), water and ethanol (equatorial cis), and two nitrate ions (axial trans). The chirality arises from
a pyrimidine−Cd2+ helical array and is preserved not only in each crystal via homochiral interstrand water−nitrate hydrogen bonding but also in all the crystals in the same chirality as a result of single-colony homochiral
crystal growth. Compound 1 also forms achiral (Pbca) trihydrate adduct 1·Cd(NO3)2·3H2O (3) having nonhelical
pyrimidine−Cd2+ zigzag chains. Achiral zigzag polymer 3 and chiral helical polymer 2 are interconvertible
with each other in the solid states upon exchange of volatile ligands (ethanol and water). The helix winding
associated with the conversion of adduct 3 to 2 can be made homochiral by seeding.
Number- and size-controlled macromolecular associations are common in biology with viruses as a typical example. We report here a novel example of artificial viruses, in which the double-helical DNA is coated with 4-nm sized neutral glycocluster nanoparticles (GNPs) with a coating stoichiometry of approximately 2 GNPs per helical pitch (10 base pairs), where GNP arises from micellization of a cone-shaped, quadruple-chain glycocluster amphiphile having eight saccharide moieties with beta-glucoside termini on the calix[4]resorcarene macrocycle. The resulting "glycoviruses" are compactly packed (54 nm in the case of 7040 base-pair plasmid pCMVluc), are well charge-shielded (zeta congruent with approximately 0 mV), and effectively transfect cell cultures without notable cytotoxicity. The use of artificial viral vectors thus allows a new (nonamine/noncationic/nonpolymeric) access to gene delivery, a potential but still tough subject which has been studied extensively over the last 15 years by using viral or amine-based cationic vectors. The remarkable adhesion-manipulation ability of saccharide clusters also provides a strategy of bottom-up construction of nanometric or mesoscopic sizes.
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 (approximately 50 nm) and well charge-shielded (zeta approximately equal 0 mV), undergo saccharide-dependent (alpha-Glc > beta-Gal >> 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 approximately 10(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.
Molecular chaperone-like activity for protein refolding was investigated using nanogels of self-assembly of cholesterol-bearing pullulan. Nanogels e¡ectively prevented protein aggregation (i.e. carbonic anhydrase and citrate synthase) during protein refolding from GdmCl denaturation. Enzyme activity recovered in high yields upon dissociation of the gel structure in which the proteins were trapped, by the addition of cyclodextrins. The nanogels assisted protein refolding in a manner similar to the mechanism of molecular chaperones, namely by catching and releasing proteins. The nanogels acted as a host for the trapping of refolded intermediate proteins. Cyclodextrin is an e¡ector molecule that controls the binding ability of these host nanogels to proteins. The present nanogel system was also e¡ective at the renaturation of inclusion body of a recombinant protein of the serine protease family.
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