Publications (9)67.53 Total impact
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Article: Nanogel-based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Pneumococcus.
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ABSTRACT: To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine-delivery system based on a nanometer-sized hydrogel (nanogel) bearing a cationic cholesteryl-group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum IgG, and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection.Infection and immunity 03/2013; · 4.21 Impact Factor -
Article: Artificial chaperone polysaccharide nanogels for protein delivery: a thermodynamic study of protein-nanogel interactions using fluorescence correlation spectroscopy.
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ABSTRACT: Molecular chaperones selectively trap heat-denatured proteins or their intermediates, primarily by hydrophobic interactions, to prevent irreversible aggregation resulting from macromolecular host (molecular chaperone)-guest (protein) interactions. The molecular chaperone function is an important concept that is expected to lead to breakthroughs in drug delivery systems, especially for protein or peptide delivery in regenerative medicine, such as bone regeneration. We have reported that polysaccharide nanogels act as artificial molecular chaperones. To further clarify the molecular chaperone function of nanogels as protein carriers, the elucidation of nanogel-protein interactions are especially important. Here, we investigated the interaction of a protein with a polysaccharide nanogel using fluorescence correlation spectroscopy at variable temperatures, using fluorescence-labeled bovine serum albumin (BSA) as a model protein. In particular, thermodynamic parameters of the heat-induced complexation of protein with CHP nanogels were evaluated using the van't Hoff plot. The plot shows that the CHP nanogels strongly complexed with heat-denatured BSA. The increased hydrophobicity of the denatured, unfolded protein may prefer complexation with amphiphilic hydrogel nanoparticles over complexation with the completely folded native protein. Thermodynamic parameters suggest that the complexation is entropically driven, rather than enthalpically, under the conditions studied.Current Drug Discovery Technologies 06/2011; 8(4):308-13. -
Article: Amphiphilic polysaccharide nanoballs: a new building block for nanogel biomedical engineering and artificial chaperones.
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ABSTRACT: Enzymatically synthesized glycogen (ESG), a highly branched (1→4)(1→6)-linked α-glucan, is a new monodisperse spherical hyperbranched nanoparticle (molecular weight, 10(6)-10(7); diameter, 20-30 nm), polysaccharide nanoball. Amphiphilic ESG nanoballs were synthesized by introducing a cholesterol group to enzymatically synthesized glycogen (CHESG). CHESG assembled into a structure containing a few molecules to form cluster nanogels (approximately 35 nm in diameter) in water. The cluster nanogels were dissociated by the addition of cyclodextrin (CD) to form a supramolecular CHESG-CD nanocomplex due to complexation with the cholesterol group and CD. The CHESG nanogel showed high capacity for complexation with proteins, and the CHESG-CD nanocomplex showed high chaperone-like activity for thermal stabilization of enzymes. CHESG has great potential to become a new building block for nanogel biomedical engineering and to act as an artificial chaperone for protein engineering.ACS Nano 01/2011; 5(1):337-45. · 10.77 Impact Factor -
Article: Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.
Nature Material 07/2010; · 32.84 Impact Factor -
Article: The binding of pullulan modified cholesteryl nanogels to Abeta oligomers and their suppression of cytotoxicity.
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ABSTRACT: Among various hydrogels able to form monodisperse and stable nanoparticles (20-30 nm) are those with pullulan-bearing cholesteryl moieties (CHP). These nanoparticles can interact with soluble proteins through hydrophobic bonding. The objectives of this study were to investigate whether CHP nanogels would interact with oligomeric forms of the 42 amino acid variant of beta-amyloid (Abeta(1-42)) and if the formation of CHP-Abeta(1-42) oligomer entities will reduce cytotoxicity of Abeta(1-42) in primary cortical cells and microglial (N9) cells. By employing fluorescent CHP analogs with different charges we provide evidence that, (i) both neutral and positively charged CHP nanoparticles interact with Abeta(1-42) monomers and oligomers, (ii) neutral CHP is non-toxic, but positively charged derivatives (CHPNH2) are toxic, particularly in primary cortical cultures, and (iii) binding of both monomeric and oligomeric Abeta(1-42) to CHP significantly reduces Abeta(1-42) toxicity in both the primary cortical and microglial cells. These results suggest that CHP nanogels could provide a valid complementary approach to antibody immunotherapy in neurological disorders characterized by the formation of soluble toxic aggregates, such as those in Alzheimer's disease (AD).Biomaterials 08/2009; 30(29):5583-91. · 7.40 Impact Factor -
Article: Structure of an unsaturated fatty acid with unique vicinal dimethyl branches isolated from the Okinawan soft coral of the genus Sinularia.
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ABSTRACT: A new unsaturated fatty acid with unique vicinal dimethyl branches was isolated from the Okinawan soft coral of the genus Sinularia. The structure of the compound was determined based on the results of spectroscopic analysis and chemical conversion. The absolute configuration was deduced by applying the Ohrui-Akasaka method.CHEMICAL & PHARMACEUTICAL BULLETIN 06/2008; 56(6):861-3. · 1.59 Impact Factor -
Article: Stolonilactone, a novel terpenoid-related compound, isolated from the Okinawan soft coral Clavularia koellikeri.
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ABSTRACT: A novel terpenoid-related compound, stolonilactone (1), was isolated from the Okinawan soft coral Clavularia koellikeri. The structure of 1 was elucidated on the basis of spectroscopic analysis. A possible biogenesis of 1 through the [4 + 2]-cycloaddition of a trisnorsesquiterpenoid-type diene and a cembranolide-type dienophile is proposed.The Journal of Organic Chemistry 07/2004; 69(13):4351-5. · 4.45 Impact Factor -
Article: Role of sulfoquinovosyl diacylglycerol for the maintenance of photosystem II in Chlamydomonas reinhardtii.
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ABSTRACT: The physiological role of sulfoquinovosyl diacylglycerol (SQDG) in photosynthesis was investigated with a SQDG defective mutant (hf-2) of Chlamydomonas reinhardtii that did not have any detectable amount of SQDG. The mutant showed a lower rate of photosystem II (PSII) activity by approximately 40% and also a lower growth rate than those of the wild-type. Results of genetical analysis of hf-2 strongly suggest that the SQDG defect and the lowered PSII activity are due to a single gene mutation. The supplementation of SQDG to hf-2 cells restored the lowered PSII activity to the same level as that of wild-type cells, and also enabled the mutant to grow even in the presence of 135 nm 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Moreover, the incubation of isolated thylakoid membranes of hf-2 with SQDG raised the lowered PSII activity. Chemical modifications of SQDG impaired the recovery of PSII activity. The results suggest that SQDG is indispensable for PSII activity in Chlamydomonas by maintaining PSII complexes in their proper state.European Journal of Biochemistry 06/2002; 269(9):2353-8. · 3.58 Impact Factor -
Article: Strongylodiols A, B and C, new cytotoxic acetylenic alcohols isolated from the Okinawan marine sponge of the genus Strongylophora as each enantiomeric mixture with a different ratio
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ABSTRACT: Three new cytotoxic long-chain acetylenic alcohols, strongylodiols A, B and C, were isolated from the Okinawan marine sponge of the genus Strongylophora. Their gross structures were elucidated based on spectroscopic analysis. During the process for determination of the absolute stereochemistry at C-6 using the modified Mosher's method, these acetylenic alcohols were each found to be an enantiomeric mixture with a different ratio; 91:9 for strongylodiol A, 97:3 for strongylodiol B and 84:16 for strongylodiol C. The R configuration for each major enantiomer was established by the modified Mosher's method. Each enantiomer was separated and fully characterized.Tetrahedron Letters 41(48):9271-9276. · 2.68 Impact Factor
