Recognition of Superpotent Sweetener Ligands by a Library of Monoclonal Antibodies

Monoclonal antibodies (mAb) made to the superpotent guanidino sweet tasting ligand, N-(p-cyanophenyl)-N-(diphenylmethyl)-guanidineacetic acid were examined for their molecular recognition specificities using 14 different sweetener analogues in a competitive radioimmunoassay. The effects of variations in pH on ligand binding was also examined by radioimmunoassay. Photoaffinity labelling of the binding site was accomplished using a radiolabelled azido-derivative of the parent ligand, and L-chain or H-chain labelling was easily identified in several different mAb. For two of the mAb examined in this study (NC6.8 and NC10.14), the analogue binding studies are in agreement with the known Fab-ligand crystal structures. Monoclonal antibodies to this family of sweet tasting compounds may be useful probes for the study of sweet taste chemistry and identification of novel sweet taste ligands from combinatorial chemical libraries. © 1997 John Wiley & Sons, Ltd.     

Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors: SAR and in vivo efficacy in hyperalgesia pain model

A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE₂ release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F = 33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model.     

Twisted Perylene Diimides with Tunable Redox Properties for Organic Sodium‐Ion Batteries

Organic rechargeable batteries gain huge scientific interest owing to the design flexibility and resource renewability of the active materials. However, the low reduction potentials still remain a challenge to compete with the inorganic cathodes. This study demonstrates a simple and efficient approach to tune the redox properties of perylene diimides (PDIs) as high voltage cathodes for organic‐based sodium‐ion batteries (SIBs). With appropriate electron‐withdrawing groups as substituents on perylene diimides, this study shows a remarkable tunability in the discharge potential from 2.1 to 2.6 V versus Na⁺/Na with a sodium intake of ≈1.6 ions per molecule. Further, this study explores tuning the shape of the voltage profiles by systematically tuning the dihedral angle in the perylene ring and demonstrates a single plateau discharge profile for tetrabromo‐substituted perylene diimide (dihedral angles θ₁ & θ₂ = 38°). Detailed structural analysis and electrochemical studies on substituted PDIs unveil the correlation between molecular structure and voltage profile. The results are promising and offer new avenues to tailor the redox properties of organic electrodes, a step closer toward the realization of greener and sustainable electrochemical storage devices.     

Influence of medium components and fermentation conditions on the production of bacteriocin(s) by Bacillus licheniformis AnBa9

Recently, antibacterial peptides are gaining more attention as an alternative therapeutics and food and other products from spoilage and deterioration. Antibacterial peptide producing strains were isolated from sediments of slaughterhouse sewage wastes. One among them, identified as Bacillus licheniformis inhibited the growth of several gram positive bacteria. Response surface methodology with central composite rotary design was used for optimization of fermentation medium and conditions for antibacterial peptide production. Lactose, NH(4)NO(3), yeast extract and NaCl and environmental factors such as pH, temperature and incubation period were selected as variables. Among ingredients, high concentration of yeast extract and NaCl had a positive effect on antibacterial peptide production and specific activity, respectively. Alkaline pH and high temperature favoured the production of antibacterial peptide by B. licheniformis AnBa9. Under optimized condition, B. licheniformis AnBa9 produced 25-fold higher production of antibacterial peptide than the un-optimized condition. Biochemical characteristics of the antibacterial peptides of B. licheniformis AnBa9 revealed that they are of bacteriocin type.     

Extraction of RNA from Ca-alginate-encapsulated yeast for transcriptional profiling

We have developed a method for preparing high-quality total RNA from Ca-alginate-encapsulated Saccharomyces cerevisiae that is suitable for microarray analysis. Encapsulated cells were harvested from immobilized cell reactors and flash-frozen in liquid nitrogen. Following low-temperature mechanical disruption, cells were freed from Ca-alginate by reverse ionotropic gelation and purified by centrifugation, and then total RNA was extracted using hot acid phenol. The yield and quality of the RNA were consistently high; the RNA was free of contaminating alginate, and in microarray analysis it performed as well as RNA isolated from planktonic cells.     

Influence of Tl+ activator ions on the luminescence characteristics of KCl0.5Br0.5:Eu2+ powder phosphors

Photoluminescence (PL) of thallium co‐doped with KCl_0.5Br_0.5:Eu²⁺ powder phosphors display emission bands at 320 and 370 nm attributable to centres involving Tl⁺ ions in addition to characteristic Eu²⁺ emission around 420 nm. Additional PL excitation and emission bandS observed around 260 and 380 nm, respectively, were observed in the double‐doped KCl_0.5Br_0.5:Eu²⁺, Tl⁺ powder phosphors and are attributed to complex centres involving Tl⁺ and Eu²⁺ ions. The enhancement observed in the intensity of Eu²⁺ emission around 420 nm with the addition of TlBr in KCl_0.5Br_0.5:Eu²⁺ powder phosphors is attributed to the energy transfer from Tl⁺ → Eu²⁺ ions. Photostimulated luminescence (PSL) studies of γ‐irradiated KCl_0.5Br_0.5:Eu²⁺, Tl⁺ mixed phosphors are reported and a tentative PSL mechanism in the phosphors has been suggested. Copyright © 2009 John Wiley & Sons, Ltd.     

Marker-assisted improvement of bacterial blight resistance in parental lines of Pusa RH10, a superfine grain aromatic rice hybrid

Pusa RH10, the widely cultivated superfine grain aromatic rice hybrid, and its parental lines Pusa6B and PRR78 are susceptible to bacterial blight (BB) disease caused by Xanthomonas oryzae pv. oryzae. Pusa1460, a Basmati rice variety, was utilized as the donor for introgressing BB resistance genes xa13 and Xa21 into Pusa6B and PRR78 using a marker-assisted backcross breeding program. The markers RG136 and pTA248 linked to BB resistance genes xa13 and Xa21, respectively, were used for foreground selection. Seventy-four STMS markers polymorphic between Pusa6B and Pusa1460, and 54 STMS markers polymorphic between PRR78 and Pusa1460, were utilized for background selection to recover the recurrent parent genome ranging from 85.14 to 97.30% and 87.04 to 92.81% in the 10 best BC₂F₅ families of Pusa6B and PRR78, respectively. RM6100, an STMS marker linked to fertility restorer gene (Rf), was used for marker-assisted selection of Rf gene in an improved version of PRR78. The extent of donor segments in the improved version of Pusa6B was estimated to be <0.97 and <2.15 Mb in the genomic regions flanking xa13 and Xa21, respectively, whereas in improved PRR78, it was estimated to be <2.07 and <3.45 Mb in the corresponding genomic regions. Improved lines of Pusa6B and PRR78 showed yield advantages of up to 8.24 and 5.23%, respectively. The performance of the BB-resistant version of Pusa RH10 produced by intercrossing the improved parental lines was on a par with or superior to the original Pusa RH10.     

Effect of H4R antagonist N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamides and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole on histamine and 4-methylhistamine-induced mast cell response

Context: The histamine plays a decisive role in acute and chronic inflammatory responses and is regulated through its four types of distinct receptors designated from H1 to H4. Recently histamine 4 receptor (H4R) antagonists have been reported to possess various pharmacological effects against various allergic diseases.

Objective: To investigate the inhibitory effect of N-(2-aminoethyl)-5-chloro-1H-indol-2-carboxamide (Compound A) and 5-chloro-2-(piperazin-1-ylmethyl)-1H-benzimidazole (Compound L) on H4R-mediated calcium mobilization, cytokine IL-13 production, ERK1/2, Akt and NF-κB activation in human mastocytoma cells-1 (HMC-1).

Materials and methods: Compounds A and L were synthesized chemically and their inhibitory effect on intracellular calcium release was analyzed by Fluo-4 calcium assay, cytokine measurement through ELISA and activation of signaling molecules by western blot.

Results: Pre-treatment with compounds A and L significantly reduced the H4R-mediated intracellular calcium release. Histamine and 4-methylhistamine (4-MH) induced Th2 cytokine IL-13 production in HMC-1 cells, was inhibited by compound A (77.61%, 74.25% at 1?μM concentration) and compound L (79.63%, 81.70% at 1?μM concentration). Furthermore, histamine induced the phosphorylation of ERK1/2, Akt and NF-κB was suppressed by compounds A and L at varying levels, ERK1/2 (88%, 86%), Akt (88%, 89%) and NF-κB (89%, 87%) in HMC-1 cells.

Discussion and conclusions: Taken together these data demonstrate that compound A and compound L may block H4R-mediated downstream signaling events.