Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We determined and compared the human receptor binding affinities and ...functional characteristics of asenapine and several antipsychotic drugs. Compounds were tested under comparable assay conditions using cloned human receptors. In comparison with the antipsychotics, asenapine showed high affinity and a different rank order of binding affinities (pK
i) for serotonin receptors (5-HT1A 8.6, 5-HT1B 8.4, 5-HT2A 10.2, 5-HT2B 9.8, 5-HT2C 10.5, 5-HT 5 8.8, 5-HT6 9.6 and 5-HT7 9.9), adrenoceptors (α1 8.9, α2A 8.9, α2B 9.5 and α2C 8.9), dopamine receptors (D1 8.9, D 2 8.9, D3 9.4 and D4 9.0) and histamine receptors (H1 9.0 and H2 8.2). It had much lower affinity (pK
i ≤ 5) for muscarinic receptors and was the only agent with affinity for H2 receptors. Relative to its D2 receptor affinity, asenapine had a higher affinity for 5-HT 2C, 5-HT2A, 5-HT2B, 5-HT7, 5-HT 6, α2B and D3 receptors, suggesting stronger engagement of these targets at therapeutic doses. Asenapine behaved as a potent antagonist (pK
B) at 5-HT1A (7.4), 5-HT 1B (8.1), 5-HT2A (9.0), 5-HT2B (9.3), 5-HT 2C (9.0), 5-HT6 (8.0), 5-HT7 (8.5), D2 (9.1), D3 (9.1), α2A (7.3), α2B (8.3), α2C (6.8) and H1 (8.4) receptors. These functional effects differed from those of risperidone (pK
B < 5 for 5-HT6) and olanzapine (pK
B < 5 for 5-HT 1A and α2). Our results indicate that asenapine has a unique human receptor signature, with binding affinity and antagonistic properties that differ appreciably from those of antipsychotic drugs.
Colloids are responsible for undesirable haze formation in wine. Here, we characterized 20 colloid batches after isolation by ultrafiltration of musts and wines from five cultivars obtained from four ...consecutive vintages. Polysaccharide and protein concentrations of the colloids ranged from 0.10 to 0.65 and 0.03 to 0.40 mg/L, respectively. Protein profiling in must and wine colloids by fast protein liquid chromatography (FPLC) and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS) analyses indicated a lower number of proteins in wine than in must colloids. Molar mass distribution analyses revealed all colloids to consist of two carbohydrate- (424-33,390 and 48-462 kg/mol) and one protein-rich (14-121 kg/mol) fractions. The observed barely negative ζ potentials (-3.1 to -1.1 mV) in unstable wines unraveled that colloid instability might be partly related to their poor electrostatic repulsion in the wine matrix. ζ potentials of the colloids from pH 1 to 10 are also presented. Our data support future developments to eliminate haze-forming colloids from wine.
In this review, we aim to present, discuss and clarify our current understanding regarding the prediction of possible antipsychotic effects of metabotropic glutamate (mGlu) receptor ligands. The ...number of preclinical trials clearly indicates, that this group of compounds constitutes an excellent alternative to presently used antipsychotic therapy, being effective not only to positive, but also negative and cognitive symptoms of schizophrenia. Although the results of clinical trials that were performed for the group of mGlu2/3 agonists were not so enthusiastic as in animal studies, they still showed that mGlu ligands do not induced variety of side effects typical for presently used antipsychotics, and were generally well tolerated. The lack of satisfactory effectiveness towards schizophrenia symptoms of mGlu2/3 activators in humans could be a result of variety of uncontrolled factors and unidentified biomarkers different for each schizophrenia patient, that should be taken into consideration in the future set of clinical trials. The subject is still open for further research, and the novel classes of mGlu5 or mGlu2/3 agonists/PAMs were recently introduced, including the large group of compounds from the third group of mGlu receptors, especially of mGlu4 subtype. Finally, more precise treatment based on simultaneous administration of minimal doses of the ligands for two or more receptors, seems to be promising in the context of symptoms-specific schizophrenia treatment.
Textiles represent promising support materials for enzymes. The goal of the present work was to investigate the immobilization of commercial peroxidase on a polyester needle felt and the repeated use ...in the gentle degradation of norbixin in whey from dairy cheese as a practical application. High enzyme loads were obtained by a 2-step immobilization procedure. First, the number of functional groups on the textile surface was increased by a modification with amino-functional polyvinylamine. Second, the enzyme was immobilized by using 2 types of crosslinking agents. Due to the iron content of peroxidase, inductively coupled plasma–optical emission spectrometry was used for the quantitative determination of the enzyme load on the textile. The enzyme activity was evaluated using common 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulfonic acid) assay for peroxidases. By the variation of enzyme input and crosslinker concentration, a maximal enzyme load of 80 mg/g of textile was achieved, and a maximum specific activity of 57 U/g of textile. For the visualization of the enzyme on the fiber surface, fluorescence microscopy as well as scanning probe microscopy were used. The immobilized peroxidase showed significant activity, even after 50 reuse cycles. In addition, the potential of the new support and enzyme combination in commercial whey bleaching was demonstrated successfully on a 10-L scale.
► Continuous foam fractionation with real fungal culture broth in stripping mode. ► Design of Experiments used to determine influencing parameters and interactions. ► Target enzyme cutinase ...efficiently separated. ► Foam fractionation could be tailored to different separation requirements.
In biotechnological processes, foaming often represents an undesired complication. Foam may induce cell death, and may limit the performance of down-stream processing steps. On the other hand, the differences in foamability of compounds can be used for separation of these substances. The process based on this principle is called foam fractionation, and has been subject of increased attention in recent years. Foam fractionation was employed for several separation tasks, for instance, the concentration of plant secondary metabolites. However, very few studies dealt with the systematic determination of significant operating parameters and their influence on the efficiency of continuous foam fractionation processes only. In this study, the influence of process parameters, like pH value or gas flow rate, were investigated on continuous foam fractionation of a fungal cutinase in stripping mode. Therefore, a Design of Experiments (DoE) was used to indicate significant parameters and their interactions. After the optimization of the foam fractionation process by means of the DoE, a maximal recovery of 98% active enzyme (enrichment: 5.6) or a maximal enrichment of 9.8 of cutinase (recovery: 79%) could be achieved.
