Highly Stereoselective Biocatalytic Synthesis of Key Cyclopropane Intermediate to Ticagrelor

Extending the scope of biocatalysis to important non-natural reactions such as olefin cyclopropanation will open new opportunities for replacing multistep chemical syntheses of pharmaceutical intermediates with efficient, clean, and highly selective enzyme-catalyzed processes. In this work, we engineered the truncated globin of Bacillus subtilis for the synthesis of a cyclopropane precursor to the antithrombotic agent ticagrelor. The engineered enzyme catalyzes the cyclopropanation of 3,4-difluorostyrene with ethyl diazoacetate on a preparative scale to give ethyl-(1R, 2R)-2-(3,4-difluorophenyl)-cyclopropanecarboxylate in 79% yield, with very high diastereoselectivity (>99% dr) and enantioselectivity (98% ee), enabling a single-step biocatalytic route to this pharmaceutical intermediate

Direct enzymatic esterification of cotton and Avicel with wild-type and engineered cutinases

In this work, the surface of cellulose, either Avicel or cotton fabric, was modified using cutinases without any previous treatment to swell or to solubilise the polymer. Aiming further improvement of cutinase ester synthase activity on cellulose, an engineered cutinase was investigated. Wild-type cutinase from Fusarium solani and its fusion with the carbohydrate-binding module N1 from Cellulomonas fimi were able to esterify the hydroxyl groups of cellulose with distinct efficiencies depending on the acid substrate/solvent system used, as shown by titration and by ATR-FTIR. The carbonyl stretching peak area increased significantly after enzymatic treatment during 72 h at 30 °C. Cutinase treatment resulted in relative increases of 31 and 9 % when octanoic acid and vegetable oil were used as substrates, respectively. Cutinase-N1 treatment resulted in relative increases of 11 and 29 % in the peak area when octanoic acid and vegetable oil were used as substrates, respectively. The production and application of cutinase fused with the domain N1 as a cellulose ester synthase, here reported for the first time, is therefore an interesting strategy to pursuit.This work was co-funded by the European Social Fund through the management authority POPH and FCT, Postdoctoral fellowship reference: SFRH/BPD/47555/2008. The authors also want to thank Doctor Raul Machado for his valuable help on FTIR spectral data treatment

Carboxylic ester hydrolases from hyperthermophiles

Carboxylic ester hydrolyzing enzymes constitute a large group of enzymes that are able to catalyze the hydrolysis, synthesis or transesterification of an ester bond. They can be found in all three domains of life, including the group of hyperthermophilic bacteria and archaea. Esterases from the latter group often exhibit a high intrinsic stability, which makes them of interest them for various biotechnological applications. In this review, we aim to give an overview of all characterized carboxylic ester hydrolases from hyperthermophilic microorganisms and provide details on their substrate specificity, kinetics, optimal catalytic conditions, and stability. Approaches for the discovery of new carboxylic ester hydrolases are described. Special attention is given to the currently characterized hyperthermophilic enzymes with respect to their biochemical properties, 3D structure, and classification

Narcissism: a factor behind the selective sharing of news online

The current study examined the extent to which narcissism influences the social network users’ intention to share positive and negative life events with (close or unknown) online contacts. Using an online survey, small vignettes and a cross-sectional convenience sample of 119 participants, the results showed that narcissism positively predicted sharing intention of positive and negative life events with strangers. However, individuals rating higher in narcissism were less likely to share negative news with family. The research findings suggest that personality traits such as narcissism, the type of contacts online, and the nature of the news may shape what information is shared by online users. The type of news presented may therefore be a function of who is posting the content, their personality, and the kind of social network contacts they have online

A thermodynamic study of ketoreductase-catalyzed reactions 3. Reduction of 1-phenyl-1-alkanones in non-aqueous solvents

The equilibrium constants K for the reactions (1-phenyl-1-alkanone + 2-propanol = 1-phenyl-1-alkanol + acetone) in the solvents n-pentane and n-hexane have been determined by using gas chromatography at the temperature 298.15 K. The 1-phenyl-1-alkaones included in this study were: 1-phenyl-1-ethanone, 1-phenyl-1-propanone, 1-phenyl-1-butanone, 1-phenyl-1-pentanone, 1-phenyl-1-hexanone, and 1-phenyl-1-heptanone. The equilibrium constants for the reaction involving 1-phenyl-1-ethanone were measured in the solvent n-hexane as a function of temperature (288 K to 308 K). The calculated thermodynamic quantities for the 1-phenyl-1-ethanone reaction at T = 298.15 K are: K = 0.2177 ± 0.0018; the standard molar Gibbs free energy change, ∆rGmo=(3.78±0.02)kJ·mol-1, the standard molar enthalpy change, ∆rHmo=(4.53±0.87)kJ·mol-1, and the standard molar entropy change, ∆rSmo=(2.5±2.9)J·K-1·mol-1. The equilibrium constants of 1-phenyl-1-alkanone with an odd number of carbons in alkyl side chain are higher than the equilibrium constants of the preceding 1-phenyl-1-alkanone having an even number of carbons in the side chain and follow a zig-zag pattern with increasing carbon number in the alkyl side chain.© Elsevie

Ideological group persuasion: A within-person study of how violence, interactivity, and credibility features influence online persuasion

Ideological groups (both non-violent and violent) make extensive use of the Internet for recruiting and other purposes, yet little is known about the effectiveness of the influence of websites of differing ideologies on attitudes and behavior. Furthermore, although credibility and interactivity have been extensively studied in online settings, they have received scant attention with regards to ideological groups. Using a within-subjects design, this study explored how individuals' attitudes, emotional reactions, behaviors and behavioral intentions are affected by two separate websites, with one promoting a liberal ideology and one promoting a conservative ideology. Results indicated that individuals preferred the liberal ideology, that violent websites led to higher negative affect and lowered perceptions of credibility than the non-violent websites, and that violence decreased the likelihood of taking action. Additionally, high interactivity increased the salience of the credibility manipulations with regards to their impact on the likelihood of taking action

The European Bioelectromagnetic Center

info:eu-repo/semantics/publishe

Notification pending: Online social support from close and nonclose relational ties via Facebook

Previous research in computer-mediated communication’s effect on social networks has generated questions about the role of weak ties in what was assumed to be a unique affordance of strong ties—obtaining effective social support. Eighty-eight college students completed a questionnaire based on their most recent Facebook status updates and the comments and likes those updates generated. Items queried participants’ perception of each response as well as the participants’ relationships characteristics with the responder. Strong ties were perceived to have significantly closer relationships and provided significant social support. However, weak tie relationships were more numerous than strong ties and were perceived by participants to provide social support that was equally significant. While the use of Facebook did not erode the importance of strong ties, this study found that traditional understandings of weak ties do not account for the strong social support afforded by weak tie relationships when mediated through social network sites

Synthesis, structure and activity of artificial, rationally designed catalytic polypeptides

BIOLOGICAL macromolecules with catalytic activity can be created artificially using two approaches. The first exploits a system that selects a few catalytically active biomolecules from a large pool of randomly generated (and largely inactive) molecules. Catalytic antibodies1 and many catalytic RNA molecules2 are obtained in this way. The second involves rational design of a biomolecule that folds in solution to present to the substrate an array of catalytic functional groups3–8. Here we report the synthesis of rationally designed polypeptides that catalyse the decarboxylation of oxaloacetate via an imine intermediate. We determine the secondary structures of the polypeptides by two-dimensional NMR spectroscopy. We are able to trap and identify intermediates in the catalytic cycle, and to explore the kinetics in detail. The formation of the imine by our artificial oxaloacetate decarboxylases is three to four orders of magnitude faster than can be achieved with simple amine catalysts: this performance rivals that of typical catalytic antibodies