O → S Acyl Transfer Directing Human Sera Glycoprotein Immobilization for Breast Cancer Diagnosis.

Breast cancer (BC) is one of the most common malignancies in the world with aberrantly expressed glycans. The different types and stages still limit a comprehensive method in the prediagnosis of BC patients. In this research, a synthetic boronic acid-disulfide (BASS) probe has been developed for the two steps of O → S → N acyl transfer in glycoprotein recognition and labeling. The specificity and sensitivity of this method have been carefully studied in the case of immunoglobulin G, and the labeling efficiency was determined up to 60%. The BASS-functionalized slide is a powerful platform for monitoring the alteration of glycan patterns in human sera. Compared to the samples from healthy individuals, sera of BC patients gave specific patterns to eight lectins binding. The BASS-directed glycoprotein strategy promises a rapid sensing platform for a high-throughput screening of clinical BC samples and could be easily applied to other cancer prediagnoses.

Responsive fluorescence enhancement for in vivo Cu(II) monitoring in zebrafish larvae.

Several neurodegenerative diseases are ascribed to disorders caused by the secretion of Cu ions. However, a majority of the current techniques for copper ion detection are restricted to in vivo monitoring and nonspecific interactions. Their methods are limited to the systematic analysis of Cu ions in living organisms. Thus, a synthetic molecular fluorophore, 5-amino 2,3-dihydroquinolinimine (NDQI), has been developed and successfully utilized in in vivo monitoring of the distribution of Cu(II) in zebrafish larvae. The reversible formation of the NDQI-Cu complex allows its use with high metal concentrations and in oxidative stress conditions. The NDQI-directed strategy developed here can quantitatively differentiate cells with different Cu(II) concentrations. Remarkably, dynamic distribution of Cu(II) in the intestine and liver can be observed.

Direct Screening of Glycan Patterns from Human Sera: A Selective Glycoprotein Microarray Strategy.

Protein glycosylation is one of the most complicated but significant post-translational modifications. Minor alterations in glycan structure can considerably affect the biology of a cell. Therefore, direct monitoring of glycan patterns of glycoproteins is closely related to cancer progression as well as metastasis. In this study, a boronic acid (BA)-tosyl-directed strategy to selectively immobilize glycoproteins on glass slides was successfully developed even in the presence of high-abundant nonglycosylated proteins. To enhance the immobilization efficiency and reduce the undesired nonspecific absorption, the strain-promoted alkyne azide cycloaddition (SPAAC) conjugation chemistry and surface blocking conditions were carefully optimized for the collection of reliable data. The optimized glycoprotein microarray platform describes specific lectin-recognition patterns of glycoproteins of interest in E. coil lysate and fetal bovine serum (FBS), which encourages us for direct monitoring of glycan patterns from human sera without tedious sample preparation. Three serum groups comprised of healthy controls and lung cancer and pancreatic cancer patients were analyzed by this new technique. Remarkably, the distinguishable glycan patterns of the three groups make them a powerful platform for cancer screening and prediagnosis.

Adaptable Fast Relaxing Boronate-Based Hydrogels for Probing Cell-Matrix Interactions.

Hydrogels with tunable viscoelasticity hold promise as materials that can recapitulate many dynamic mechanical properties found in native tissues. Here, covalent adaptable boronate bonds are exploited to prepare hydrogels that exhibit fast relaxation, with relaxation time constants on the order of seconds or less, but are stable for long-term cell culture and are cytocompatible for 3D cell encapsulation. Using human mesenchymal stem cells (hMSC) as a model, the fast relaxation matrix mechanics are found to promote cell-matrix interactions, leading to spreading and an increase in nuclear volume, and induce yes-associated protein/PDZ binding domain nuclear localization at longer times. All of these effects are exclusively based on the hMSCs' ability to physically remodel their surrounding microenvironment. Given the increasingly recognized importance of viscoelasticity in controlling cell function and fate, it is expected that the synthetic strategies and material platform presented should provide a useful system to study mechanotransduction on and within viscoelastic environments and explore many questions related to matrix biology.

Synthesis and Photophysical Characterization of 2,3-Dihydroquinolin-4-imines: New Fluorophores with Color-Tailored Emission.

In this study, a series of variously substituted 2,3-dihydroquinolin-4-imines (DQIs) were synthesized from N-substituted propargylanilines by copper(I)-catalyzed annulation. The approach adopted in this study under mild, effective conditions exhibited broad substrate tolerance, particularly for functional groups substituted on anilines. Most of the DQI derivatives synthesized under optimal conditions were obtained in good isolated yields of 63-88 %. 2,3-Dihydroquinolinimine thus obtained was easily converted to important structures like 2,3-dihydroquinolone and tetrahydrobenzodiazepin-5-one, confirming the importance of this strategy in constructing various heterocycles. Surprisingly, 2,3-dihydroquinolinimines thus obtained exhibited bright fluorescence with quantum yields up to 66 %. The density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed for understanding the excited-state nature of DQI system. Accordingly, a tailored DQI derivative bearing methoxy group at C-6 position and acetoxy group at C-7 position was designed and synthesized to give emission at 559 nm with redshift compared to the 7-methoxy substituted DQI. A detailed study of DQI structures with their photophysical properties was performed with five control molecules and consequently demonstrated the uniqueness of the chemical structures of DQIs.

Thermally Induced Denitrogenative Annulation for the Synthesis of Dihydroquinolinimines and Chroman-4-imines.

A rapid growth in synthetic methods for the preparation of diverse organic molecules using N-sulfonyl-1,2,3-triazoles is of great interest in organic synthesis. Transition metals are generally used to activate the α-imino diazo intermediates. Metal-free methods have not been studied in detail, but can be a good complement to transition metal catalysis in the mild reaction conditions. We herein report a novel method for the preparation of 2,3-dihydroquinolin-4-imine and chroman-4-imine analogs from their corresponding N-sulfonyl-1,2,3-triazoles in the absence of metal catalysts. To achieve intramolecular annulation, the introduction of an electron-donating group is required at the meta position of N-sulfonyl-1,2,3-triazole methyl anilines. The inclusion of tailored substituents on the aniline moieties and nitrogen atoms enhances the nucleophilicity of the phenyl π-electrons, thus allowing them to undergo a Friedel-Crafts-type reaction with the highly electrophilic ketenimines. This metal-free method was carefully optimized to generate a variety of dihydroquinolin-4-imines and chroman-4-imines in moderate-to-good yields.