Antibody therapies that bind to PD1 protein and inhibit its binding with PDL1 protein have shown unprecedented clinical success in activating innate immune system to treat cancer. Here, the authors investigated activity of several macrocyclic compounds in inhibiting PD1-PDL1 interaction, leading to identification of Rifabutin, an approved macrocyclic antibiotic, as top active compound with remarkable IC50 value of ~25 µM. Computational docking followed by molecular dynamics simulations revealed Rifabutin making key interactions with PD1, occupying and blocking majority of the area on PD1 protein where PDL1 is known to bind.
The authors developed a novel cryogenic milling technique in liquid nitrogen (LN2) using dry ice beads. The contamination issue related to fragments of eroded beads could be overcome due to their spontaneous removal. In this study, the transformation process from the pellets and the morphological change of dry ice beads during milling process in LN2 was monitored to assess their potential as milling media. The authors presented that dry ice could maintain its bead shape even under vigorous agitation in LN2. Further, they demonstrated that their milling performance was comparable to conventional technique using zirconia beads.
The authors developed a rapid and efficient analytical technique for cyclosporine A using HPLC. Under optimized conditions, cyclosporine A was separated with high resolution from other cyclic peptides within 3 min, because the mass transfer resistance in the stationary phase was reduced by the use of the small, nonporous particle columns. The results indicate that cyclosporine A is structurally rigid and undergoes poor water solvation even at high temperature. In the context of the rapid development of cyclic peptides with similar physicochemical characteristics to cyclosporine A, the developed method is useful for the development of cyclic peptide therapeutics.
Fuligocandin B isolated from the slime mold Fuligo candida induced apoptosis in TRAIL resistance cancer cells by increasing death receptor 5 (DR5) thorough binding to valosin-containing protein (VCP). Heterocyclic derivatives of fuligocandin B were synthesized and evaluated. Amine derivative designed based on docking simulation showed potent cytotoxicity against TRAIL resistance human gastric adenocarcinoma (AGS) cells. The figure represents picture of Fuligo candida, structure of 7’-amino fuligocandin B and image of increasing DR5 which goes to bind to TRAIL on the cell surface.
Carotenoid Stereochemistry Affects Antioxidative Activity of Liposomes Co-encapsulating Astaxanthin and Tocotrienol
公開日: 2018/07/01 | 66 巻 7 号 p. 714-720
Misuzu Ishikawa, Shota Hirai, Tatsusada Yoshida, Natsumi Shibuya, Susumu Hama, Yu Takahashi, Tatsuya Fukuta, Tamotsu Tanaka, Shinzo Hosoi, Kentaro Kogure
New Methods and Reagents in Organic Synthesis. 14. A Simple Efficient Preparation of Methyl Esters with Trimethylsilyldiazomethane (TMSCHN2) and Its Application to Gas Chromatographic Analysis of Fatty Acids
公開日: 2008/03/31 | 29 巻 5 号 p. 1475-1478
橋本 典夫, 青山 豊彦, 塩入 孝之