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991.
Sanhita Sinharay Gabriela Fernández‐Cuervo Jasmine P. Acfalle Mark D. Pagel 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(19):6491-6495
A chemical exchange saturation transfer (CEST) MRI contrast agent has been developed that detects sulfatase enzyme activity. The agent produces a CEST signal at δ=5.0 ppm before enzyme activity, and a second CEST signal appears at δ=9.0 ppm after the enzyme cleaves a sulfate group from the agent. The comparison of the two signals improved detection of sulfatase activity. 相似文献
992.
M. Sc. Nikolaos Eleftheriadis M. Sc. Stephanie A. Thee M. Sc. Martijn R. H. Zwinderman Dr. Niek G. J. Leus Prof. Frank J. Dekker 《Angewandte Chemie (International ed. in English)》2016,55(40):12300-12305
Human 15‐lipoxygenase‐1 (15‐LOX‐1) plays an important role in several inflammatory lung diseases, such as asthma, COPD, and chronic bronchitis, as well as various CNS diseases, such as Alzheimer's disease, Parkinson's disease, and stroke. Activity‐based probes of 15‐LOX‐1 are required to explore the role of this enzyme further and to enable drug discovery. In this study, we developed a 15‐LOX‐1 activity‐based probe for the efficient activity‐based labeling of recombinant 15‐LOX‐1. 15‐LOX‐1‐dependent labeling in cell lysates and tissue samples was also possible. To mimic the natural substrate of the enzyme, we designed activity‐based probes that covalently bind to the active enzyme and include a terminal alkene as a chemical reporter for the bioorthogonal linkage of a detectable functionality through an oxidative Heck reaction. The activity‐based labeling of 15‐LOX‐1 should enable the investigation and identification of this enzyme in complex biological samples, thus opening up completely new opportunities for drug discovery. 相似文献
993.
Design of Potent Mannose 6‐Phosphate Analogues for the Functionalization of Lysosomal Enzymes To Improve the Treatment of Pompe Disease 下载免费PDF全文
Afitz Da Silva Dr. Coralie Bernon Dr. Pierre Cérutti Dr. Frédéric Salgues Marc Perez Dr. Marie Maynadier Dr. Magali Gary‐Bobo Dr. Catherine Caillaud Dr. Martine Cérutti Dr. Marcel Garcia Prof. Alain Morère 《Angewandte Chemie (International ed. in English)》2016,55(47):14774-14777
Improving therapeutics delivery in enzyme replacement therapy (ERT) for lysosomal storage disorders is a challenge. Herein, we present the synthesis of novel analogues of mannose 6‐phosphate (M6P), known as AMFAs and functionalized at the anomeric position for enzyme grafting. AMFAs are non‐phosphate serum‐resistant derivatives that efficiently bind the cation‐independent mannose 6‐phosphate receptor (CI‐M6PR), which is the main pathway to address enzymes to lysosomes. One of the AMFAs was used to improve the treatment of the lysosomal myopathy Pompe disease, in which acid α‐glucosidase (GAA) is defective. AMFA grafting on a M6P‐free recombinant GAA led to a higher uptake of the GAA in adult Pompe fibroblasts in culture as compared to Myozyme, the M6P recombinant GAA. Moreover, the treatment of Pompe adult mice with the AMFA‐grafted recombinant enzyme led to a remarkable improvement, even at low doses, in muscle functionality and regeneration, whereas Myozyme had limited efficacy. 相似文献
994.
Dr. Elvira Romero Dr. J. Rubén Gómez Castellanos Prof. Dr. Andrea Mattevi Prof. Dr. Marco W. Fraaije 《Angewandte Chemie (International ed. in English)》2016,55(51):15852-15855
Cyclohexanone monooxygenase (CHMO) is a promising biocatalyst for industrial reactions owing to its broad substrate spectrum and excellent regio‐, chemo‐, and enantioselectivity. However, the low stability of many Baeyer–Villiger monooxygenases is an obstacle for their exploitation in industry. Characterization and crystal structure determination of a robust CHMO from Thermocrispum municipale is reported. The enzyme efficiently converts a variety of aliphatic, aromatic, and cyclic ketones, as well as prochiral sulfides. A compact substrate‐binding cavity explains its preference for small rather than bulky substrates. Small‐scale conversions with either purified enzyme or whole cells demonstrated the remarkable properties of this newly discovered CHMO. The exceptional solvent tolerance and thermostability make the enzyme very attractive for biotechnology. 相似文献
995.
996.
建立了双抗体夹心酶联免疫法检测蓖麻毒素的方法。优化了最佳蓖麻毒素多克隆抗体包被浓度和包被方法、蓖麻毒素单克隆抗体工作浓度、酶标记二抗体工作浓度和显色时间等实验条件。方法的线性范围在1.2~10.0μg/L之间,线性回归方程y=0.05x 0.42,相关系数为0.9962,检出限为0.2μg/L。将该方法用于检测实际水样蓖麻毒素加标样品,回收率为91.7%~104.0%;检测实际土壤加标样品,回收率为83.3%~98.0%;检测奶粉加标样品,回收率为83.3%~94.0%;检测实际血液加标样品,回收率为75.0%~82.0%。 相似文献
997.
以DNA为模板,通过一步法合成了一种银铂双金属纳米簇(DNA-Ag/Pt NCs),其粒径为2~4 nm,并表现出较强的过氧化物模拟酶活性,能催化H2O2氧化TMB使溶液变蓝色。基于此特性,结合Hg2+可与胸腺嘧啶碱基形成T-Hg2+-T结构,设计研制了一种非标记的电化学传感器,用于Hg2+的灵敏特异性检测。实验结果表明,在最佳条件下,该传感器的检测范围为0.65~3.5 nmol/L,检出限达0.17 nmol/L,能较好地识别Hg2+。该传感器有望用于实际水样中痕量汞的检测。 相似文献
998.
999.
Structural and Spectroscopic Characterization of a High‐Spin {FeNO}6 Complex with an Iron(IV)−NO− Electronic Structure 下载免费PDF全文
Amy L. Speelman Dr. Bo Zhang Prof. Carsten Krebs Prof. Nicolai Lehnert 《Angewandte Chemie (International ed. in English)》2016,55(23):6685-6688
Although the interaction of low‐spin ferric complexes with nitric oxide has been well studied, examples of stable high‐spin ferric nitrosyls (such as those that could be expected to form at typical non‐heme iron sites in biology) are extremely rare. Using the TMG3tren co‐ligand, we have prepared a high‐spin ferric NO adduct ({FeNO}6 complex) via electrochemical or chemical oxidation of the corresponding high‐spin ferrous NO {FeNO}7 complex. The {FeNO}6 compound is characterized by UV/Visible and IR spectroelectrochemistry, Mössbauer and NMR spectroscopy, X‐ray crystallography, and DFT calculations. The data show that its electronic structure is best described as a high‐spin iron(IV) center bound to a triplet NO? ligand with a very covalent iron?NO bond. This finding demonstrates that this high‐spin iron nitrosyl compound undergoes iron‐centered redox chemistry, leading to fundamentally different properties than corresponding low‐spin compounds, which undergo NO‐centered redox transformations. 相似文献
1000.
Regioselective Dichlorination of a Non‐Activated Aliphatic Carbon Atom and Phenolic Bismethylation by a Multifunctional Fungal Flavoenzyme 下载免费PDF全文
Pranatchareeya Chankhamjon Dr. Yuta Tsunematsu Dr. Mie Ishida‐Ito Yuzuka Sasa Florian Meyer Dr. Daniela Boettger‐Schmidt Barbara Urbansky Klaus‐Dieter Menzel Dr. Kirstin Scherlach Prof. Dr. Kenji Watanabe Prof. Dr. Christian Hertweck 《Angewandte Chemie (International ed. in English)》2016,55(39):11955-11959
The regioselective functionalization of non‐activated carbon atoms such as aliphatic halogenation is a major synthetic challenge. A novel multifunctional enzyme catalyzing the geminal dichlorination of a methyl group was discovered in Aspergillus oryzae (Koji mold), an important fungus that is widely used for Asian food fermentation. A biosynthetic pathway encoded on two different chromosomes yields mono‐ and dichlorinated polyketides (diaporthin derivatives), including the cytotoxic dichlorodiaporthin as the main product. Bioinformatic analyses and functional genetics revealed an unprecedented hybrid enzyme (AoiQ) with two functional domains, one for halogenation and one for O‐methylation. AoiQ was successfully reconstituted in vivo and in vitro, unequivocally showing that this FADH2‐dependent enzyme is uniquely capable of the stepwise gem‐dichlorination of a non‐activated carbon atom on a freestanding substrate. Genome mining indicated that related hybrid enzymes are encoded in cryptic gene clusters in numerous ecologically relevant fungi. 相似文献