Recent advances in proteome‐wide label‐free target deconvolution for bioactive small molecules

2021 ◽  
Author(s):  
Jichao Sun ◽  
Nayana Prabhu ◽  
Jun Tang ◽  
Fan Yang ◽  
Lin Jia ◽  
...  
2018 ◽  
Vol 185 ◽  
pp. 10006 ◽  
Author(s):  
Natalia V. Guteneva ◽  
Sergey L. Znoyko ◽  
Alexey V. Orlov ◽  
Maxim P. Nikitin ◽  
Petr I. Nikitin

Precise quantitative and highly sensitive detection of small molecules (haptens) is highly demanded in medicine, food quality control, in vitro diagnostics, criminalistics, environmental monitoring, etc. In the present work, the magnetic method of particle quantification and the optical methods of spectral correlation and spectral phase interferometry complement each other for optimization of a quantitative assay for measuring concentrations of small molecules. The assay employs magnetic nanoparticles as labels in rapid immunochromatographic format. The approach was demonstrated with fluorescein as a model molecule. The interferometric label-free biosensors were employed for selection of optimal reagents that produced high specificity and sensitivity. The method of magnetic particle quantification counted the magnetic labels over the entire volume of the immunochromatographic membrane to provide their distribution along the test strip. Such distribution was used for optimization of such parameters as concentrations of the used reagents and of antibody immobilized on the labels, amount of the labels and conjugates of haptens with protein carriers to realize the advanced quantitative immunochromatographic assay.


2020 ◽  
Author(s):  
Rhushabh Maugi ◽  
bernadette gamble ◽  
david bunka ◽  
Mark Platt

A universal aptamer-based sensing strategy is proposed using DNA modified nanocarriers and Resistive Pulse Sensing for the rapid and label free detection of small molecules. The surface of a magnetic nanocarrier was first modified with a ssDNA aka linker which is designed to be partially complimentary in sequence to a ssDNA aptamer. The aptamer and linker form a stable dsDNA complex on the nanocarriers surface. Upon the addition of the target molecule, a conformational change takes place where the aptamer preferentially binds to the target over the linker; causing the aptamer to be released into solution. The RPS measures the change in velocity of the nanocarrier as its surface changes from dsDNA to ssDNA, and its velocity is used as a proxy for the concentration of the target. We illustrate the versatility of the assay by demonstrating the detection of the antibiotic Moxifloxacin, and chemotherapeutics Imatinib and Irinotecan.


2020 ◽  
pp. mcp.R120.002095 ◽  
Author(s):  
Daniel G Delafield ◽  
Lingjun Li

Growing implications of glycosylation in physiological occurrences and human disease have prompted intensive focus on revealing glycomic perturbations through absolute and relative quantification. Empowered by seminal methodologies and increasing capacity for detection, identification, and characterization, the past decade has provided a significant increase in the number of suitable strategies for glycan and glycopeptide quantification. Mass spectrometry-based strategies for glycomic quantitation have grown to include metabolic incorporation of stable isotopes, deposition of mass difference and mass defect isotopic labels, and isobaric chemical labeling, providing researchers with ample tools for accurate and robust quantitation. Beyond this, workflows have been designed to harness instrument capability for label-free quantification and numerous software packages have been developed to facilitate reliable spectrum scoring. In this review, we present and highlight the most recent advances in chemical labeling and associated techniques for glycan and glycopeptide quantification.


Micromachines ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 744 ◽  
Author(s):  
Xiangchun Xuan

Magnetic field-induced particle manipulation is simple and economic as compared to other techniques (e.g., electric, acoustic, and optical) for lab-on-a-chip applications. However, traditional magnetic controls require the particles to be manipulated being magnetizable, which renders it necessary to magnetically label particles that are almost exclusively diamagnetic in nature. In the past decade, magnetic fluids including paramagnetic solutions and ferrofluids have been increasingly used in microfluidic devices to implement label-free manipulations of various types of particles (both synthetic and biological). We review herein the recent advances in this field with focus upon the continuous-flow particle manipulations. Specifically, we review the reported studies on the negative magnetophoresis-induced deflection, focusing, enrichment, separation, and medium exchange of diamagnetic particles in the continuous flow of magnetic fluids through microchannels.


2020 ◽  
Vol 12 (21) ◽  
pp. 2674-2681
Author(s):  
Fatemeh Shafiei ◽  
Kathleen McAuliffe ◽  
Yousef Bagheri ◽  
Zhining Sun ◽  
Qikun Yu ◽  
...  

A paper-based portable fluorogenic RNA sensor for the selective, sensitive, and rapid detection of target analytes.


Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5702
Author(s):  
Quentin T. L. Pasquer ◽  
Ioannis A. Tsakoumagkos ◽  
Sascha Hoogendoorn

Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against a target or phenotype of interest. Especially in the case of phenotypic screening approaches, a major challenge is to translate the compound-induced phenotype into a well-defined cellular target and mode of action of the hit compound. There is no “one size fits all” approach, and recent years have seen an increase in available target deconvolution strategies, rooted in organic chemistry, proteomics, and genetics. This review provides an overview of advances in target identification and mechanism of action studies, describes the strengths and weaknesses of the different approaches, and illustrates the need for chemical biologists to integrate and expand the existing tools to increase the probability of evolving screen hits to robust chemical probes.


Nanoscale ◽  
2015 ◽  
Vol 7 (17) ◽  
pp. 7763-7769 ◽  
Author(s):  
Ana S. Peinetti ◽  
Helena Ceretti ◽  
Martín Mizrahi ◽  
Graciela A. González ◽  
Silvana A. Ramírez ◽  
...  

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