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Dr. Timo Broese Dr. Peter Ehlers Dr. Peter Langer Dr. Jan von Langermann 《Chembiochem : a European journal of chemical biology》2021,22(23):3314-3318
Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield. 相似文献
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Friederike Freiin von Hvel Ekaterini Kefalakes Claudia Grothe 《International journal of molecular sciences》2021,22(1)
Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems. 相似文献
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Dr. Raysa Khan Tareque Dr. Storm Hassell-Hart Dr. Tobias Krojer Dr. Anthony Bradley Dr. Srikannathasan Velupillai Dr. Romain Talon Dr. Michael Fairhead Dr. Iain J. Day Kamlesh Bala Dr. Robert Felix Dr. Paul D. Kemmitt Prof. Paul Brennan Prof. Frank von Delft Dr. Laura Díaz Sáez Prof. Kilian Huber Prof. John Spencer 《ChemMedChem》2020,15(24):2513-2520
Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified. 相似文献
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Nur Lina Rashidah Mohd Rashid Abdullah Abdul Samat Abdul Azim Jais Mahendra Rao Somalu Andanastuti Muchtar Nurul Akidah Baharuddin Wan Nor Roslam Wan Isahak 《Ceramics International》2019,45(6):6605-6615
The performance of low-to-intermediate temperature (400–800?°C) solid oxide fuel cells (SOFCs) depends on the properties of electrolyte used. SOFC performance can be enhanced by replacing electrolyte materials from conventional oxide ion (O2-) conductors with proton (H+) conductors because H+ conductors have higher ionic conductivity and theoretical electrical efficiency than O2- conductors within the target temperature range. Electrolytes based on cerate and/or zirconate have been proposed as potential H+ conductors. Cerate-based electrolytes have the highest H+ conductivity, but they are chemically and thermally unstable during redox cycles, whereas zirconate-based electrolytes exhibit the opposite properties. Thus, tailoring the properties of cerate and/or zirconate electrolytes by doping with rare-earth metals has become a main concern for many researchers to further improve the ionic conductivity and stability of electrolytes. This article provides an overview on the properties of four types of cerate and/or zirconate electrolytes including cerate-based, zirconate-based, single-doped cerate–zirconate and hybrid-doped cerate–zirconate. The properties of the proton electrolytes such as ionic conductivity, chemical stability and sinterability are also systematically discussed. This review further provides a summary of the performance of SOFCs operated with cerate and/or zirconate proton conductors and the actual potential of these materials as alternative electrolytes for proton-conducting SOFC application. 相似文献
6.
Dr. Lina Liang Tong-You Wade Wei Pei-Yu Wu Wouter Herrebout Ming-Daw Tsai Prof. Stéphane P. Vincent 《Chembiochem : a European journal of chemical biology》2020,21(20):2982-2990
d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant. 相似文献
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Dovile Stravinskiene Aiste Sliziene Lina Baranauskiene Vilma Petrikaite Aurelija Zvirbliene 《International journal of molecular sciences》2020,21(24)
Monoclonal and recombinant antibodies are widely used for the diagnostics and therapy of cancer. They are generated to interact with cell surface proteins which are usually involved in the development and progression of cancer. Carbonic anhydrase XII (CA XII) contributes to the survival of tumors under hypoxic conditions thus is considered a candidate target for antibody-based therapy. In this study, we have generated a novel collection of monoclonal antibodies (MAbs) against the recombinant extracellular domain of CA XII produced in HEK-293 cells. Eighteen out of 24 MAbs were reactive with cellular CA XII on the surface of live kidney and lung cancer cells as determined by flow cytometry. One MAb 14D6 also inhibited the enzymatic activity of recombinant CA XII as measured by the stopped-flow assay. MAb 14D6 showed the migrastatic effect on human lung carcinoma A549 and renal carcinoma A498 cell lines in a ‘wound healing’ assay. It did not reduce the growth of multicellular lung and renal cancer spheroids but reduced the cell viability by the ATP Bioluminescence assay. Epitope mapping revealed the surface-exposed amino acid sequence (35-FGPDGENS-42) close to the catalytic center of CA XII recognized by the MAb 14D6. The variable regions of the heavy and light chains of MAb 14D6 were sequenced and their complementarity-determining regions were defined. The obtained variable sequences were used to generate recombinant antibodies in two formats: single-chain fragment variable (scFv) expressed in E. coli and scFv fused to human IgG1 Fc fragment (scFv-Fc) expressed in Chinese Hamster Ovary (CHO) cells. Both recombinant antibodies maintained the same specificity for CA XII as the parental MAb 14D6. The novel antibodies may represent promising tools for CA XII-related cancer research and immunotherapy. 相似文献
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