Glycosyldisulfides from dynamic combinatorial libraries as O-glycoside mimetics for plant and endogenous lectins: their reactivities in solid-phase and cell assays and conformational analysis by molecular dynamics simulations

Dynamic combinatorial library design exploiting the thiol-disulfide exchange readily affords access to glycosyldisulfides. In order to reveal lectin-binding properties of this type of non-hydrolyzable sugar derivative, libraries originating from a mixture of common building blocks of natural glycans and thiocompounds were tested against three plant agglutinins with specificity to galactose, fucose or N-acetylgalactosamine, respectively, in a solid-phase assay. Extent of lectin binding to matrix-immobilized neoglycoprotein presenting the cognate sugar could be reduced, and evidence for dependence on type of carbohydrate was provided by dynamic deconvolution. Glycosyldisulfides also maintained activity in assays of increased physiological relevance, that is, using native tumor cells and also adding to the test panel an endogenous lectin (galectin-3) involved in tumor spread and cardiac dysfunction. N-Acetylgalactosamine was pinpointed as the most important building block of libraries for the human lectin and the digalactoside as most potent compound acting on the toxic mistletoe agglutinin which is closely related to the biohazard ricin. Because this glycosyldisulfide, which even surpasses lactose in inhibitory capacity, rivals thiodigalactoside as inhibitor, their degrees of intramolecular flexibility were comparatively analyzed by computational calculations. Molecular dynamics runs with explicit consideration of water molecules revealed a conspicuously high degree of potential for shape alterations by the disulfide's three-bond system at the interglycosidic linkage. The presented evidence defines glycosyldisulfides as biologically active ligands for lectins.     

Synthesis, structures and magnetic properties of two self-assembly uniform nets (10,3), containing three-connected nodes

Two three-dimensional (3D) coordination polymers {[NaFe(dipic)₂(H₂O)₂]}_∞ (1) and {[NaCr(dipic)₂(H₂O)₂]}_∞ (2) containing Fe₅Na₅ and Cr₅Na₅ mixed d-/s-block subunits were synthesized by the reactions of tridentate ligand H₂dipic (pyridine-2,6-dicarboxylic acid) with Fe(ClO₄)₃ · 6H₂O or Cr(ClO₄)₃ · 6H₂O through the self-assembly process with sodium ions. The X-ray diffraction analyses reveal that both complexes have 3D (10,3) topology. Magnetic susceptibility measurements of both complexes in the temperature range of 2-300 K reveal the occurrence of weak antiferromagnetic interactions together with zero-field splitting effects.     

Allelochemicals released by rice roots and residues in soil

A few rice (Oryza sativa L.) varieties or rice straw produce and release allelochemicals into soil in which interfere with the growth of neighboring or successive plants. Allelopathic rice PI312777 and Huagan-1 at their early growth stages released momilactone B, 3-isopropyl-5-acetoxycyclohexene-2-one-1, and 5,7,4′-trihydroxy-3′,5′-dimethoxyflavone into soil at phytotoxic levels, but non-allelopathic rice Huajingxian did not. Both allelopathic and non-allelopathic rice residues released momilactone B and lignin-related phenolic acids (p-hydroxybenzoic, p-coumaric, ferulic, syringic and vanillic acids) into the soil during residue decomposition to inhibit successive plants. The results indicated that allelochemicals involved in rice allelopathy from living and dead plants are substantially different. Interestingly, the concentrations of the allelochemicals released from the allelopathic rice seedlings in soil increased dramatically when they were surrounded with Echinochloa crus-galli. The concentrations of the allelochemicals were over 3-fold higher in the presence of E. crus-galli than in the absence of E. crus-galli. However, the same case did not occur in non-allelopathic Huajingxian seedlings surrounded with E. crus-galli. In addition to allelochemical exudation being promoted by the presence of E. crus-galli, allelopathic rice seedlings also increased allelochemical exudation in response to exudates of germinated E. crus-galli seeds or lepidimoide, an uronic acid derivative exuded from E. crus-galli seeds. These results imply that allelopathic rice seedlings can sense certain allelochemicals released by E. crus-galli into the soil, and respond by increased production of allelochemicals inhibitory to E. crus-galli. This study suggests that rice residues of both allelopathic and non-allelopathic varieties release similar concentrations and types of allelochemicals to inhibit successive plants. In contrast, living rice plants of certain allelopathic varieties appear to be able to detect the presence of interspecific neighbors and respond by increased allelochemicals.     

An improved route to the synthetic of diphenyl alpha-(diethoxythiophosphorylamino)methylphosphonates

An improved method for the synthesis of Diphenyl alpha-(diethoxythiophosphorylamino)methylphosphonates under mild conditions is described. It consists of the reaction of diethyl thiophosphoramidate (1) with triphenyl phosphite (3) and a substituted benzylaldehyde or ketone (2) by a one-pot procedure with the aid of acetyl chloride.     

Structure diversity of silver(I) [1,1′-bis(diphenylphosphino)cobaltocenium] complexes: Effect of counteranions

Single crystal X-ray structural characterizations are recorded for an array of adducts of the form {AgX:[dppc][PF₆]}_n (n = 1 or 2), [dppc][PF₆] = 1,1′-bis(diphenylphosphino)cobaltocenium hexafluorophosphate, X = Cl, Br, NO₃, NO₂, C₆H₅CO₂, CF₃CO₂. Synthetic procedures for all adducts are reported. All compounds have been fully characterised by elemental analysis and spectroscopic techniques. The structures in the solid state were found to depend on the nature of the counterion, for X = NO₃, NO₂, the complex being monomeric {[dppc-P,P′]Ag(NO₃)₂} or {[dppc-P,P′]Ag(NO₂)}, for X = Cl, Br, C₆H₅CO₂, CF₃CO₂, the complex is a dimer.     

Two 3D noninterpenetrated chiral coordination polymers with uniform (10)-srs and (4.6.8)-sra nets

Two new noninterpenetrated three-dimensional chiral coordination polymers [Cu(l-cys)(H₂O)]_n (1) and [Cd(l-cys)(H₂O)]_n (2) (where H₂cys = cysteic acid) have been synthesized and characterized using single-crystal X-ray diffraction, elemental analysis, infrared spectroscopy, and thermogravimetric analysis. In the two complexes, l-cys acts as a μ₃-bridge for 1 and a μ₄-bridge for 2, respectively, to link metal centers in different modes, forming two different three-dimensional networks. The topological analysis of them shows that 1 can be simplified to a three-connected topology with the short symbol of 10³ and the full vertex symbol of 10₅.10₅.10₅ while 2 a four-connected topology with the short symbol of 4².6³.8 and the full vertex symbol of 4.6.4.6.6.8₂, respectively.     

Molecular Mechanism of Inward Rectifier Potassium Channel 2.3 Regulation by Tax-Interacting Protein-1

Inwardly rectifying potassium channel 2.3 (Kir2.3) is specifically targeted on the basolateral membranes of epithelial and neuronal cells, and it thus plays an important role in maintaining potassium homeostasis. Tax-interacting protein-1 (TIP-1), an atypical PDZ-domain-containing protein, binds to Kir2.3 with a high affinity, causing the intracellular accumulation of Kir2.3 in cultured epithelial cells. However, the molecular basis of the TIP-1/Kir2.3 interaction is still poorly understood. Here, we present the crystal structure of TIP-1 in complex with the C-terminal Kir2.3-peptide (residues 436-445) to reveal the molecular details of the interaction between them. Moreover, isothermal titration calorimetry experiments show that the C-terminal Kir2.3-peptide binds much more strongly to TIP-1 than to mammalian Lin-7, indicating that TIP-1 can compete with mammalian Lin-7 to uncouple Kir2.3 from its basolateral membrane anchoring complex. We further show that the phosphorylation/dephosphorylation of Ser443 within the C-terminal Kir2.3 PDZ-binding motif RRESAI dynamically regulates the Kir2.3/TIP-1 association in heterologous HEK293T cells. These data suggest that TIP-1 may act as an important regulator for the endocytic pathway of Kir2.3.     

HBXIP upregulates CD46, CD55 and CD59 through ERK1/2/NF-κB signaling to protect breast cancer cells from complement attack

Hepatitis B X-interacting protein (HBXIP) is able to enhance migration of breast cancer cells. However, the role of HBXIP in regulation of complement-dependent cytotoxicity (CDC) in breast cancer is not understood. Here, we report that HBXIP contributes to protecting breast cancer cells from CDC by upregulating membrane-bound complement regulatory protein (mCRPs), including CD46, CD55 and CD59. We found that HBXIP upregulated mCRPs through activating p-ERK1/2/NF-κB. Interestingly, the knockdown of CD59 was able to block the HBXIP-enhanced breast tumor growth in animal. Thus, we conclude that HBXIP upregulates CD46, CD55 and CD59 through p-ERK1/2/NF-κB signaling to protect breast cancer from CDC.