Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2

1. Download : Download high-res image (273KB)
2. Download : Download full-size image

Highlights? CPYPP binds to DOCK2 DHR-2 domain and inhibits its catalytic activity ? CPYPP inhibits DOCK2-mediated Rac activation in cells ? The structural features of CPYPP required for its inhibitory effect were revealed ? CPYPP inhibits lymphocyte migration and activation in vitro and in vivo     

Synthesis of the Carbohydrate Moiety of Glycoproteins from the Parasite Echinococcus granulosus and Their Antigenicity against Human Sera

Stereocontrolled syntheses of biotin-labeled oligosaccharide portions containing the carbohydrate moiety of glycoprotein from Echinococcus granulosus have been accomplished. Trisaccharide Galβ1-3Galβ1-3GalNAcα1-R (A), tetrasaccharide Galα1-4Galβ1-3Galβ1-3GalNAcα1-R (B), and pentasaccharide Galα1-4Galβ1-3Galβ1-3Galβ1-3GalNAcα1-R (C), (R = biotinylated probe) were synthesized by stepwise condensation and/or block synthesis by the use of 5-(methoxycarbonyl)pentyl 2-azido-4,6-O-benzylidene-2-deoxy-α-d-galactopyranoside as a common glycosyl acceptor. The synthesis of the tetrasaccharide and the pentasaccharide was improved from the viewpoint of reducing the number of synthetic steps and increasing the total yield by changing from stepwise condensation to block synthesis. Moreover, hexasaccharide E, which contains the oligosaccharide sequence which occurs in E. granulosus, was synthesized from trisaccharide D. We examined the antigenicity of these five oligosaccharides by an enzyme-linked immunosorbent assay (ELISA). Although compounds of C–E did not exhibit antigenicity against cystic echinococcosis (CE) patient sera, compounds B, D, and E showed good serodiagnostic potential for alveolar echinococcosis (AE).     

Chemical syntheses of lipid X and lipid Y,acyl glucosamine 1-phosphates isolated from escherichia coli mutants

Two new phospholipids, 2-N; 3-O-bis (R)-3-hydroxytetradecanoyl-glucosamine 1-phosphate and 2-N-(R) -3-hexadecanoyloxytetradecanoyl-3-O-(R)-3-hydroxytetradecanoylglucosamine 1-phosphate, were synthesized and identified with natural lipid X and lipid Y respectively.     

Strain‐Induced Double Carbon–Carbon Bond Activations of Cycloparaphenylenes by a Platinum Complex: Application to the Synthesis of Cyclic Diketones

The carbon–carbon (C?C) bond activation of [n]cycloparaphenylenes ([n]CPPs) by a transition‐metal complex is herein reported. The Pt⁰ complex Pt(PPh₃)₄ regioselectively cleaves two C?C σ bonds of [5] CPP and [6]CPP to give cyclic dinuclear platinum complexes in high yields. Theoretical calculations reveal that the relief of ring strain drives the reaction. The cyclic complex was further transformed into a cyclic diketone by using a CO insertion reaction.     

Photochemistry of some alkoxycarbonylplatinum(II) complexes

Alkoxycarbonylplatinum(II) complexes trans-Pt(CO₂CH₂R)Cl(PPh₃)₂, where R = H, Me and Ph, were synthesized in two steps and were characterized by infrared and ultraviolet absorption, proton and phosphorus-31 nuclear magnetic resonance, and mass spectral techniques, and by elemental analysis. Irradiation of the complexes in the solid state or in fluid solution with 254 nm light causes a steady decrease in the intensities of the infrared absorptions in the 1650 and 1070 cm^?1 regions, which is interpreted as signifying labilization of the alkoxycarbonyl ligand. In dichloromethane solution, irradiation causes dissociation of the alkoxycarbonyl ligand, which then decomposes into carbon monoxide and an alkoxide ion. The carbon monoxide is thought to re-coordinate to afford the stable product trans-PtCl(CO)(PPh₃)₂⁺. In the presence of oxygen, triphenylphosphine which dissociates from the metal, is photooxidized to form triphenylphosphine oxide in a parallel photoreaction. Disappearance quantum yields for the alkoxycarbonyl complexes are quite small, Φ ～ 10^?4?10^?3 mol/einstein, and follow the trend H > Me > Ph.     

Synthesis and antitumor activity of lipid A analogs having a phosphonooxyethyl group with alpha- or beta-configuration at position 1

Three novel lipid A analogs, which have an alpha- or beta-glycosidically bound phosphonooxyethyl group instead of the alpha-glycosyl phosphate group of natural lipid A, were synthesized. The first analog (2) had an alpha-phosphonooxyethyl group on the identical acylated disaccharide 4'-phosphate structure found in natural lipid A (from Escherichia coli) and hence differed from the latter only in the nature of the acidic group at position 1. The second one (3) had tetradecanoyl groups in place of the two (R)-3-hydroxytetradecanoyl groups bound to the 2- and 3-hydroxyl function of 2, retaining the alpha-phosphonooxyethyl group. The structure of the third analog (4) was the same as that of 3 except that the phosphonooxyethyl group of the former was beta-oriented. Compounds 2 and 3 exhibited potent activity against Meth A at the same level as natural lipid A, whereas 4 showed less activity. This fact revealed that the glycosidic phosphate is not a prerequisite for the antitumor activity of lipopolysaccharide. It can be replaced with a phosphonooxyethyl group without any loss of activity provided that the alpha-anomeric configuration at C-1 is retained. The replacement of the hydroxytetradecanoyl groups with tetradecanoyl groups does not change the activity either.     

Structure of arnebifuranone,new monoterpenylbenzoquinone from arnebia euchroma

A new monoterpenylbenzoquinone named arnebifuranone (5) was isolated from arnebiaeuchroma (Royle) Johnst. and its structure was elucidated to be a 2,3-dimethoxy-1,4-benzoquinone having a monoterpene side chain containing a furan ring. The monoterpene moiety is bonded to the benzoquinone ring with its head carbon.     

A rapid and reliable solid-phase extraction method for high-performance liquid chromatographic analysis of opium alkaloids from papaver plants

A rapid and reliable solid-phase extraction method for HPLC analysis of opium alkaloids from Papaver plants was established. Fifty mg of dried and powdered plant sample was extracted with 5 ml of 5% acetic acid for 30 min under sonication. After centrifugation, 3 ml of the supernatant was loaded on a reversed-phase cation-exchange solid-phase extraction cartridge. After seriate washings with 0.1 M hydrochloric acid and methanol, alkaloids were eluted with a mixture of 28% ammonia and methanol (1:19). The eluate was concentrated under nitrogen stream at 40 degrees C and the residue was dissolved in 50% aqueous methanol for high performance liquid chromatographic analysis. With this solid-phase extraction method, the recovery of morphine, codeine, oripavine, thebaine, papaverine, noscapine and sanguinarine was from 99.94 to 112.18% when the standard alkaloids were added to the plant samples. Opium alkaloids of a variety of genus Papaver plants cultivated in a field and phytotron were analyzed by this method.     

Total synthesis of escherichia coli lipid A

The first total synthesis of E. coli lipid A ($\text{1}$) is described. The synthetic compound was identical with a natural specimen and exhibited the full endotoxic activity. It was thus conclusively proved by this chemical synthesis that lipid A is the active principle of bacterial endotoxin.