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21.
Tao Wang Dr. Yuzhou Wu Dr. Seah Ling Kuan Oliver Dumele Dr. Markus Lamla Dr. David Y. W. Ng Matthias Arzt Jessica Thomas Jan O. Mueller Prof. Dr. Christopher Barner‐Kowollik Prof. Dr. Tanja Weil 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(1):228-238
A disulfide intercalator toolbox was developed for site‐specific attachment of a broad variety of functional groups to proteins or peptides under mild, physiological conditions. The peptide hormone somatostatin (SST) served as model compound for intercalation into the available disulfide functionalization schemes starting from the intercalator or the reactive SST precursor before or after bioconjugation. A tetrazole–SST derivative was obtained that undergoes photoinduced cycloaddition in mammalian cells, which was monitored by live‐cell imaging. 相似文献
22.
In Situ Proteome Profiling and Bioimaging Applications of Small‐Molecule Affinity‐Based Probes Derived From DOT1L Inhibitors 下载免费PDF全文
Biwei Zhu Dr. Hailong Zhang Sijun Pan Chenyu Wang Dr. Jingyan Ge Prof. Dr. Jun‐Seok Lee Prof. Dr. Shao Q. Yao 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(23):7824-7836
DOT1L is the sole protein methyltransferase that methylates histone H3 on lysine 79 (H3K79), and is a promising drug target against cancers. Small‐molecule inhibitors of DOT1L such as FED1 are potential anti‐cancer agents and useful tools to investigate the biological roles of DOT1L in human diseases. FED1 showed excellent in vitro inhibitory activity against DOT1L, but its cellular effect was relatively poor. In this study, we designed and synthesized photo‐reactive and “clickable” affinity‐based probes (AfBPs), P1 and P2 , which were cell‐permeable and structural mimics of FED1 . The binding and inhibitory effects of these two probes against DOT1L protein were extensively investigated in vitro and in live mammalian cells (in situ). The cellular uptake and sub‐cellular localization properties of the probes were subsequently studied in live‐cell imaging experiments, and our results revealed that, whereas both P1 and P2 readily entered mammalian cells, most of them were not able to reach the cell nucleus where functional DOT1L resides. This offers a plausible explanation for the poor cellular activity of FED1 . Finally with P1 / P2 , large‐scale cell‐based proteome profiling, followed by quantitative LC‐MS/MS, was carried out to identify potential cellular off‐targets of FED1 . Amongst the more than 100 candidate off‐targets identified, NOP2 (a putative ribosomal RNA methyltransferase) was further confirmed to be likely a genuine off‐target of FED1 by preliminary validation experiments including pull‐down/Western blotting (PD/WB) and cellular thermal shift assay (CETSA). 相似文献
23.
Fabrication and microstructural characterization of functionally graded porous acrylonitrile butadiene styrene and the effect of cellular morphology on creep behavior 下载免费PDF全文
Farooq Al Jahwari Ahmed A. W. Anwer Hani E. Naguib 《Journal of Polymer Science.Polymer Physics》2015,53(11):795-803
The ability to control material properties in space and time for functionally graded viscoelastic materials makes them an asset where they can be adapted to different design requirements. The continuous microstructure makes them advantageous over conventional composite materials. Functionally graded porous structures have the added advantage over conventional functionally graded materials of offering a significant weight reduction compared to a minor drop in strength. Functionally graded porous structures of acrylonitrile butadiene styrene (ABS) had been fabricated with a solid‐state constrained foaming process. Correlating the microstructure to material properties requires a deterministic analysis of the cellular structure. This is accomplished by analyzing the scanning electron microscopy images with a locally adaptive image threshold technique based on variational energy minimization. This characterization technique of the cellular morphology is analyst independent and works very well for porous structures. Inferences are drawn from the effect of processing on microstructure and then correlated to creep strain and creep compliance. Creep is strongly correlated to porosity and pore sizes but more associated to the size than to porosity. The results show the potential of controlling the cellular morphology and hence tailoring creep strain/compliance of ABS to some desired values. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 795–803 相似文献
24.
A Lysosome‐Compatible Near‐Infrared Fluorescent Probe for Targeted Monitoring of Nitric Oxide 下载免费PDF全文
Baogang Wang Prof. Shichong Yu Dr. Xiaoyun Chai Prof. Tiejun Li Prof. Qiuye Wu Prof. Ting Wang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(16):5649-5656
The requirement for nitric oxide (NO) of lysosomes has motivated the development of a sophisticated fluorescent probe to monitor the distribution of this important biomolecule at the subcellular level in living cells. A near‐infrared (NIR) fluorescent Si‐rhodamine (SiRB)‐NO probe was designed based on the NO‐induced ring‐opening process of Si‐rhodamine. The probe exhibits fast chromogenic and fluorogenic responses, and high sensitivity and selectivity toward trace amounts of NO. Significantly, the spirolactam in Si‐rhodamine exhibits very good tolerance to H+, which in turn brings extremely low background fluorescence not only in the physiological environment but also under acidic conditions. The stability of the highly fluorescent product in acidic solution provides persistent fluorescence emission for long‐term imaging experiments. To achieve targeted imaging with improved spatial resolution and sensitivity, an efficient lysosome‐targeting moiety was conjugated to a SiRB‐NO probe, affording a tailored lysosome‐targeting NIR fluorescent Lyso‐SiRB‐NO probe. Inheriting the key advantages of its parent SiRB‐NO probe, Lyso‐SiRB‐NO is a functional probe that is suited for monitoring lysosomal NO with excellent lysosome compatibility. Imaging experiments demonstrated the monitoring of both exogenous and endogenous NO in real time by using the Lyso‐SiRB‐NO probe. 相似文献
25.
Multidrug‐Containing,Salt‐Based,Injectable Supramolecular Gels for Self‐Delivery,Cell Imaging and Other Materials Applications 下载免费PDF全文
Rajdip Roy Prof. Parthasarathi Dastidar 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(42):14929-14939
Both molecular and crystal‐engineering approaches were exploited to synthesize a new class of multidrug‐containing supramolecular gelators. A well‐known nonsteroidal anti‐inflammatory drug, namely, indomethacin, was conjugated with six different l ‐amino acids to generate the corresponding peptides having free carboxylic acid functionality, which reacted further with an antiviral drug, namely, amantadine, a primary amine, in 1:1 ratio to yield six primary ammonium monocarboxylate salts. Half of the synthesized salts showed gelation ability that included hydrogelation, organogelation and ambidextrous gelation. The gels were characterized by table‐top and dynamic rheology and different microscopic techniques. Further insights into the gelation mechanism were obtained by temperature‐dependent 1H NMR spectroscopy, FTIR spectroscopy, photoluminescence and dynamic light scattering. Single‐crystal X‐ray diffraction studies on two gelator salts revealed the presence of 2D hydrogen‐bonded networks. One such ambidextrous gelator (capable of gelling both pure water and methyl salicylate, which are important solvents for biological applications) was promising in both mechanical (rheoreversible and injectable) and biological (self‐delivery) applications for future multidrug‐containing injectable delivery vehicles. 相似文献
26.
Structural Manipulation of Ruthenium(II) Polypyridine Nitrone Complexes to Generate Phosphorogenic Bioorthogonal Reagents for Selective Cellular Labeling 下载免费PDF全文
Tommy Siu‐Ming Tang Dr. Hua‐Wei Liu Prof. Kenneth Kam‐Wing Lo 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(28):9649-9659
We report a new class of ruthenium(II) polypyridine complexes functionalized with a nitrone group as phosphorogenic bioorthogonal probes. These complexes were very weakly emissive owing to rapid C=N isomerization of the nitrone moiety, but exhibited significant emission enhancement upon strain‐promoted alkyne–nitrone cycloaddition (SPANC) reaction with bicyclo[6.1.0]nonyne (BCN)‐modified substrates. The modification of nitrone with a dicationic ruthenium(II) polypyridine unit at the α‐C‐position and a phenyl ring at the N‐position led to remarkably accelerated reaction kinetics, which are substantially greater (up to ≈278 fold) than those of other acyclic nitrone–BCN systems. Interestingly, the complexes achieved specific cell membrane/cytosol staining upon specific labeling of an exogenous substrate, BCN‐modified decane (BCN‐C10), in live cells. Importantly, the in situ generation of the more lipophilic isoxazoline adduct in the cytoplasm resulted in increased cytotoxicity, highlighting a novel approach to apply the SPANC labeling technique in drug activation. 相似文献
27.
A series of Mn(II) aminophosphonate complexes were successfully synthesized and intercalated into the hydroxy double salt [Zn5(OH)8]Cl2·yH2O. Complex incorporation led to an increase in the interlayer spacing from 7.8 to 10–12 Å. Infrared spectroscopy showed the presence of the characteristic vibration peaks of the Mn(II) complexes in the intercalates' spectra, indicating successful incorporation. The complex-loaded composites had somewhat lower proton relaxivities than the pure complexes. Nevertheless, these intercalates may have use as MRI contrast agents for patients with poor kidney function, where traditional Gd(III)-based contrast agents cause severe renal failure. 相似文献
28.
Dr. Joaquim Torra Dr. Felipe Viela Dr. Diego Megías Dr. Begoña Sot Prof. Cristina Flors 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(19):e202200026
CRANAD-2 is a fluorogenic curcumin derivative used for near-infrared detection and imaging in vivo of amyloid aggregates, which are involved in neurodegenerative diseases. We explore the performance of CRANAD-2 in two super-resolution imaging techniques, namely stimulated emission depletion (STED) and single-molecule localization microscopy (SMLM), with markedly different fluorophore requirements. By conveniently adapting the concentration of CRANAD-2, which transiently binds to amyloid fibrils, we show that it performs well in both techniques, achieving a resolution in the range of 45–55 nm. Correlation of SMLM with atomic force microscopy (AFM) validates the resolution of fine features in the reconstructed super-resolved image. The good performance and versatility of CRANAD-2 provides a powerful tool for near-infrared nanoscopic imaging of amyloids in vitro and in vivo. 相似文献
29.
针对深度学习训练成本高,以及基于磁共振图像的前列腺癌临床诊断需要大量医学常识且极为耗时的问题,本文提出了一种基于级联卷积神经网络(Convolutional Neural Network,CNN)和磁共振图像的前列腺癌(Prostate Cancer,PCa)自动分类诊断方法,该网络以Faster-RCNN作为前网络,对前列腺区域进行提取分割,用于排除前列腺附近组织器官的干扰;以基于ResNet改进的网络结构CNN40bottleneck作为后网络,用于对前列腺区域病变进行分类.后网络由瓶颈结构串联组成,其中使用批量标准化(Batch Normalization,BN)、全局平均池化(Global Average Pooling,GAP)进行优化.实验结果证明,本文方法对前列腺癌诊断结果较好,而且缩减了训练时间和参数量,有效降低了训练成本. 相似文献
30.
为了克服太空环境的复杂性,满足航天工程的空间使用要求,研制一款2 500万像素宽光谱共焦成像的微型星载相机光学系统。该系统适应卫星发射和在轨道运行的恶劣环境,具有抗冲击震动、耐太空高温差强辐射,体积小,质量轻等优点。设计的系统可在450 nm~800 nm的谱段内清晰成像,焦距181 mm,入瞳口径45 mm,视场角10.4°,边缘相对照度0.81,轴上点MTF:0.57@55 lp/mm,0.33@110 lp/mm,畸变1.2%,镜头质量622 g,外形尺寸Φ58.3 mm×117 mm,抗辐照性能≥5 krad。通过温度适应性的模拟和优化,用户进行?30 ℃~+70 ℃光学镜头热真空试验,可正常工作。该系统已成功应用于天宫二号伴飞卫星相机中,获得的图像清晰稳定,为空间遥感实验观测发挥了重要的作用。 相似文献