共查询到20条相似文献，搜索用时 62 毫秒
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2018,130(29):9171-9175
The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal‐to‐noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β‐galactosidase. The activation of the prodrug in the presence of β‐galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses β‐galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in β‐galactosidase‐overexpressing tumor‐bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment. 相似文献
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Dr. Qaisar Nadeem Dr. Giuseppe Meola Dr. Henrik Braband Robin Bolliger Dr. Olivier Blacque Daniel Hernández-Valdés Prof. Dr. Roger Alberto 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(3):1213-1216
The labeling of (bio)molecules with metallic radionuclides such as 99mTc demands conjugated, multidentate chelators. However, this is not always necessary since phenyl rings can directly serve as integrated, organometallic ligands. Bis-arene sandwich complexes are generally prepared by the Fischer–Hafner reaction. In extension of this, we show that [99mTc(η6-C6R6)2]+-type complexes are directly accessible from water and [99mTcO4]−, even using arenes incompatible with Fischer–Hafner conditions. To unambiguously confirm the nature of these unprecedented 99mTc complexes, their rhenium homologous have been prepared by substituting naphthalene ligands in [Re(η6-C10H8)2]+ with the corresponding phenyl groups. The ease with which highly stable [99mTc(η6-C6R6)2]+ complexes are formed under standard labeling conditions enables a multitude of new potential imaging agents based on commercial pharmaceuticals or lead structures. 相似文献
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Antonio Fernandez Emily J. Thompson Jeffrey W. Pollard Takanori Kitamura Marc Vendrell 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(47):17050-17054
We report the novel chemical design of fluorescent activatable chemokines as highly specific functional probes for imaging subpopulations of immune cells in live tumours. Activatable chemokines behave as AND‐gates since they emit only after receptor binding and intracellular activation, showing enhanced selectivity over existing agents. We have applied this strategy to produce mCCL2‐MAF as the first probe for in vivo detection of metastasis‐associated macrophages in a preclinical model of lung metastasis. This strategy will accelerate the preparation of new chemokine‐based probes for imaging immune cell function in tumours. 相似文献
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Dipanjan Pan Ewald Roessl Jens‐Peter Schlomka Shelton D. Caruthers Angana Senpan Mike J. Scott John S. Allen Huiying Zhang Grace Hu Patrick J. Gaffney Eric T. Choi Volker Rasche Samuel A. Wickline Roland Proksa Gregory M. Lanza 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2010,122(50):9829-9833
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Jiaguo Huang Yan Lyu Jingchao Li Penghui Cheng Yuyan Jiang Kanyi Pu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(49):17960-17968
Despite its high morbidity and mortality, contrast‐induced acute kidney injury (CIAKI) remains a diagnostic dilemma because it relies on in vitro detection of insensitive late‐stage blood and urinary biomarkers. We report the synthesis of an activatable duplex reporter (ADR) for real‐time in vivo imaging of CIAKI. ADR is equipped with chemiluminescence and near‐infrared fluorescence (NIRF) signaling channels that can be activated by oxidative stress (superoxide anion, O2.?) and lysosomal damage (N‐acetyl‐β‐d ‐glucosaminidase, NAG), respectively. By virtue of its high renal clearance efficiency (80 % injected doses after 24 h injection), ADR detects sequential upregulation of O2.? and NAG in the kidneys of living mice prior to a significant decrease in glomerular filtration rate (GFR) and tissue damage in the course of CIAKI. ADR outperforms the typical clinical assays and detects CIAKI at least 8 h (NIRF) and up to 16 h (chemiluminescence) earlier. 相似文献
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(45):14405-14409
Coiled‐coil peptides are frequently used to create new function upon the self‐assembly of supramolecular complexes. A multitude of coil peptide sequences provides control over the specificity and stability of coiled‐coil complexes. However, comparably little attention has been paid to the development of methods that allow the reversal of complex formation under non‐denaturing conditions. Herein, we present a reversible two‐state switching system. The process involves two peptide molecules for the formation of a size‐mismatched coiled‐coil duplex and a third, disruptor peptide that targets an overhanging end. A real‐time fluorescence assay revealed that the proximity between two chromophores can be switched on and off, repetitively if desired. Showcasing the advantages provided by non‐denaturing conditions, the method permitted control over the bivalent interactions of the tSH2 domain of Syk kinase with a phosphopeptide ligand. 相似文献
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Hang Li Pranav Balan Akos Vertes 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2016,128(48):15259-15263
Metabolism in microbial colonies responds to competing species, rapidly evolving genetic makeup, and sometimes dramatic environmental changes. Conventional characterization of the existing and emerging microbial strains and their interactions with antimicrobial agents, e.g., the Kirby–Bauer susceptibility test, relies on time consuming methods with limited ability to discern the molecular mechanism and the minimum inhibitory concentration. Assessing the metabolic adaptation of microbial colonies requires their non‐targeted molecular imaging in a native environment. Laser ablation electrospray ionization (LAESI) is an ambient ionization technique that in combination with mass spectrometry (MS) enables the analysis and imaging of numerous metabolites and lipids. In this contribution, we report on the application of LAESI‐MS imaging to gain deeper molecular insight into microbe–antibiotic interactions, and enhance the quantitative nature of antibiotic susceptibility testing while significantly reducing the required incubation time. 相似文献
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(39):11955-11958
Singlet oxygen is among the reactive oxygen species (ROS) with the shortest life‐times in aqueous media because of its extremely high reactivity. Therefore, designing sensors for detection of 1O2 is perhaps one of the most challenging tasks in the field of molecular probes. Herein, we report a highly selective and sensitive chemiluminescence probe ( SOCL‐CPP ) for the detection of 1O2 in living cells. The probe reacts with 1O2 to form a dioxetane that spontaneously decomposes under physiological conditions through a chemiexcitation pathway to emit green light with extraordinary intensity. SOCL‐CPP demonstrated promising ability to detect and image intracellular 1O2 produced by a photosensitizer in HeLa cells during photodynamic therapy (PDT) mode of action. Our findings make SOCL‐CPP the most effective known chemiluminescence probe for the detection of 1O2. We anticipate that our chemiluminescence probe for 1O2 imaging would be useful in PDT‐related applications and for monitoring 1O2 endogenously generated by cells in response to different stimuli. 相似文献
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(33):9864-9867
We report X‐ray crystallographic and 19F NMR studies of the G‐protein RhoA complexed with MgF3−, GDP, and RhoGAP, which has the mutation Arg85′Ala. When combined with DFT calculations, these data permit the identification of changes in transition state (TS) properties. The X‐ray data show how Tyr34 maintains solvent exclusion and the core H‐bond network in the active site by relocating to replace the missing Arg85′ sidechain. The 19F NMR data show deshielding effects that indicate the main function of Arg85′ is electronic polarization of the transferring phosphoryl group, primarily mediated by H‐bonding to O3G and thence to PG. DFT calculations identify electron‐density redistribution and pinpoint why the TS for guanosine 5′‐triphosphate (GTP) hydrolysis is higher in energy when RhoA is complexed with RhoGAPArg85′Ala relative to wild‐type (WT) RhoGAP. This study demonstrates that 19F NMR measurements, in combination with X‐ray crystallography and DFT calculations, can reliably dissect the response of small GTPases to site‐specific modifications. 相似文献
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