Preparation and functional analysis of gossypols having two carbohydrate appendages with enaminooxy linkages.

We developed new gossypol (Gos)-based glycoconjugates through dehydration condensation of native Gos and chemically modified glycosides having aminooxy groups. The resultant glycoconjugates (glycoGos) were resistant to hydrolysis, although they were light-sensitive and slowly decomposed even under indoor lighting. The glycoGos also exhibited improved water solubility compared with native Gos, but their saturated concentrations in water were still low (6.4-17 µM), due to their hydrophobic naphthyl rings. We also carried out WST-8 assays to assess the anticancer activity of the glycoGos on DLD-1 and HepG2 cells and found that the glycoGos having ß-lactosides and having ß-galactosides (specific ligands for asialoglycoprotein receptors) showed enhanced anticancer activity on HepG2 cells.

Radiation-induced magnetization reversal causing a large flux loss in undulator permanent magnets.

We report an unexpectedly large flux loss observed in permanent magnets in one of the undulators operated in SACLA, the x-ray free electron laser facility in Japan. Characterizations of individual magnets extracted from the relevant undulator have revealed that the flux loss was caused by a homogeneous magnetization reversal extending over a wide area, but not by demagnetization of individual magnets damaged by radiation. We show that the estimated flux-loss rate is much higher than what is reported in previous papers, and its distribution is much more localized to the upstream side. Results of numerical and experimental studies carried out to validate the magnetization reversal and quantify the flux loss are presented, together with possible countermeasures against rapid degradation of the undulator performance.

Galactose-PEG dual conjugation of beta-(1-->3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake.

Antisense oligonucleotides (AS ODNs) are applied to silence a particular gene, and this approach is one of the potential gene therapies. However, naked oligonucleotides are easy to be degraded or absorbed in biological condition. Therefore, we need a carrier to deliver AS ODNs. This paper presents galactose moieties that were conjugated to the side chain of SPG to enhance cellular ingestion through endocytosis mediated by asialoglycoprotein receptor specifically located on parenchymal liver cells. We introduced galactose with two types of chemical bonds; amide and amine, and the amine connection showed lower ingestion and more toxicity than the amide one. Since PEG was known to induce endocytosis escape, we combined PEG and galactose aiming to provide both cellular up-take and subsequent endocytosis escape. We designed lactose or galactose moieties to attach to the end of the PEG chain that connects to the SPG side chain. When the PEG had the molecular weight of 5000-6000, the antisense effect reached the maximum. We believe that this new type of galactose and PEG dual conjugation broaden the horizon in antisense delivery.

Schizophyllan-folate conjugate as a new non-cytotoxic and cancer-targeted antisense carrier.

Schizophyllan having folate-appendages was synthesized from native schizophyllan through NaIO(4)-oxidation and the subsequent reductive amination in aqueous ammonia followed by amido-coupling with folic acid. The resulting folate-appended schizophyllan can form stable complex with poly(dA), show specific affinity toward folate binding protein, and mediate effective antisense activity in cancer cells.