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News Article | May 1, 2017
Site: www.chromatographytechniques.com

Chemiluminescence, or chemical light, is the principle behind glow sticks (also known as light sticks) used at rock concerts and as quick tools to grab when the electricity goes out. But they can also be used to diagnose diseases by identifying concentrations of biological samples. A new mechanism developed by Tel Aviv University researchers produces a 3,000-times-brighter, water-resistant chemiluminescent probe with particular application to medical and cancer diagnosis. The research found that tweaking the electronic structure of current probes improves their inherent fluorescence. This could lead to the invention of a new single-component system with multiple applications -- including the detection and measurement of cellular activity that points to certain pathologies, such as cancer. The study was recently published in ACS Central Science. "Chemiluminescence is considered one of the most sensitive methods used in diagnostic testing," said Doron Shabat of TAU's School of Chemistry, who led the research. "We have developed a method to prepare highly efficient compounds that emit light upon contact with a specific protein or chemical. These compounds can be used as molecular probes to detect cancerous cells, among other applications." The research, conducted in collaboration with Christoph Bauer of Geneva University, repairs an energy-loss "glitch" in current chemiluminescent probes. Most systems use a mixture of one emitter molecule that detects the species of interest, and another two additional ingredients -- a fluorophore and a soap-like substance called a surfactant -- that amplify the signal to detectable levels. But energy is lost in the transfer process from the emitter molecule to the fluorophore, and surfactants are not biocompatible. "As synthetic chemists, we knew how to link structure and function," said Shabat. "By adding two key atoms, we created a much brighter probe than those currently on the market. In addition, this particular molecule is suitable for direct use in cells." Based on this molecule, the researchers developed sensors to detect several biologically relevant chemicals. They also used the chemiluminescent molecule to measure the activity of several enzymes and to image cells by microscopy. "This gives us a new powerful methodology with which we can prepare highly efficient chemiluminescence sensors for the detection, imaging and analysis of various cell activities," said Shabat. The researchers are currently exploring ways of amplifying the chemiluminescence of the new probes for in vivo imaging.


News Article | May 2, 2017
Site: www.rdmag.com

A novelty glow stick might hold the key to detecting cancer and other diseases. Researchers from Tel Aviv University have developed a water-resistant chemiluminescent probe that can detect and measure cellular activity that points to certain pathologies, including cancer. The researchers were able to tweak the electronic structure of current probes to improve their inherent fluorescence, which could lead to the invention of a single component system with multiple application opportunities. “Chemiluminescence is considered one of the most sensitive methods used in diagnostic testing,” professor Doron Shabat of TAU’s School of Chemistry, who led the research, said in a statement. “We have developed a method to prepare highly efficient compounds that emit light upon contact with a specific protein or chemical. “These compounds can be used as molecular probes to detect cancerous cells, among other applications,” he added. The majority of systems use a mixture of one emitter molecule that detects the species of interest, as well as a fluorophore and a soap-like substance called a surfactant that amplify the signal to detectable levels. However, the researchers repaired an energy-loss “glitch” in current chemiluminescent probes. “As synthetic chemists, we knew how to link structure and function,” Shabat said. "By adding two key atoms, we created a much brighter probe than those currently on the market. In addition, this particular molecule is suitable for direct use in cells." The researchers developed sensors that detect several biologically relevant chemicals based on the molecule used and also used the chemiluminescent molecule to measure the activity of several enzymes and to image cells by microscopy. “This gives us a new powerful methodology with which we can prepare highly efficient chemiluminescence sensors for the detection, imaging and analysis of various cell activities,” Shabat said. According to the study, chemiluminescence probes are considered to be among the most sensitive diagnostic tools that provide high signal-to-noise ratio for various applications such as DNA detection and immunoassays. The next step for the researchers is to explore ways to amplify the chemiluminescence of the new probes for in vivo imaging. The study was published in ACS Central Science.


News Article | May 1, 2017
Site: www.eurekalert.org

Chemiluminescence, or chemical light, is the principle behind the glow sticks (also known as light sticks) used at rock concerts and as quick tools to grab when the electricity goes out. But they can also be used to diagnose diseases by identifying concentrations of biological samples. A new mechanism developed by Tel Aviv University researchers produces a 3,000-times-brighter, water-resistant chemiluminescent probe with particular application to medical and cancer diagnosis. The research found that tweaking the electronic structure of current probes improves their inherent fluorescence. This could lead to the invention of a new single-component system with multiple applications -- including the detection and measurement of cellular activity that points to certain pathologies, such as cancer. The study was recently published in ACS Central Science. "Chemiluminescence is considered one of the most sensitive methods used in diagnostic testing," said Prof. Doron Shabat of TAU's School of Chemistry, who led the research. "We have developed a method to prepare highly efficient compounds that emit light upon contact with a specific protein or chemical. These compounds can be used as molecular probes to detect cancerous cells, among other applications." The research, conducted in collaboration with Dr. Christoph Bauer of Geneva University, repairs an energy-loss "glitch" in current chemiluminescent probes. Most systems use a mixture of one emitter molecule that detects the species of interest, and another two additional ingredients -- a fluorophore and a soap-like substance called a surfactant -- that amplify the signal to detectable levels. But energy is lost in the transfer process from the emitter molecule to the fluorophore, and surfactants are not biocompatible. "As synthetic chemists, we knew how to link structure and function," said Prof. Shabat. "By adding two key atoms, we created a much brighter probe than those currently on the market. In addition, this particular molecule is suitable for direct use in cells." Based on this molecule, the researchers developed sensors to detect several biologically relevant chemicals. They also used the chemiluminescent molecule to measure the activity of several enzymes and to image cells by microscopy. "This gives us a new powerful methodology with which we can prepare highly efficient chemiluminescence sensors for the detection, imaging and analysis of various cell activities," said Prof. Shabat. The researchers are currently exploring ways of amplifying the chemiluminescence of the new probes for in vivo imaging. The research was funded in part by the Israel Science Foundation, the Binational Science Foundation, the German Israeli Foundation, and the Israeli National Nanotechnology Initiative. American Friends of Tel Aviv University (AFTAU) supports Israel's most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. For three years in a row, TAU ranked 9th in the world, and first in Israel, for alumni going on to become successful entrepreneurs backed by significant venture capital, a ranking that surpassed several Ivy League universities. To date, 2,400 patents have been filed out of the University, making TAU 29th in the world for patents among academic institutions.


News Article | May 3, 2017
Site: phys.org

Researchers use fluorescence probes to monitor increases in mRNA-ribosome interaction levels for a gene associated with iron storage in response to iron (right panels). Scale bar = 20 μm. Credit: American Chemical Society Think of life as a house: if DNA molecules are blueprints, then messenger RNAs (mRNAs) are orders, describing the required parts (proteins) and when they should arrive. But putting in many orders doesn't always mean you'll get all of the parts on time—maybe there's a delay with your vendor or delivery service. Similarly, mRNA levels alone do not dictate protein levels. Today in ACS Central Science, researchers report a method to address that issue. David Tirrell, Kelly Burke and Katie Antilla note that in order to better understand how genes are regulated, one needs to see the mRNA when it is at the site of protein synthesis. Using fluorescence probes, the researchers designed a technique that shows mRNA when it comes in contact with giant protein synthesizing machines called ribosomes. They used this method to record the synthesis of proteins and to measure cellular responses to iron. Unlike previous methods, their tool works without the need to engineer an mRNA of interest. Tirrell notes that the method is applicable to essentially any type of RNA, and could be modified to visualize other types of interactions in the cell. Explore further: Researchers prove protein synthesis and mRNA degradation are structurally linked


News Article | May 3, 2017
Site: www.eurekalert.org

Think of life as a house: if DNA molecules are blueprints, then messenger RNAs (mRNAs) are orders, describing the required parts (proteins) and when they should arrive. But putting in many orders doesn't always mean you'll get all of the parts on time -- maybe there's a delay with your vendor or delivery service. Similarly, mRNA levels alone do not dictate protein levels. Today in ACS Central Science, researchers report a method to address that issue. David Tirrell, Kelly Burke and Katie Antilla note that in order to better understand how genes are regulated, one needs to see the mRNA when it is at the site of protein synthesis. Using fluorescence probes, the researchers designed a technique that shows mRNA when it comes in contact with giant protein synthesizing machines called ribosomes. They used this method to record the synthesis of proteins and to measure cellular responses to iron. Unlike previous methods, their tool works without the need to engineer an mRNA of interest. Tirrell notes that the method is applicable to essentially any type of RNA, and could be modified to visualize other types of interactions in the cell. The authors acknowledge funding from the National Science Foundation, Rose Hills Foundation, German Research Foundation and the Gordon and Betty Moore Foundation. The paper will be freely available on May 3 here: http://pubs. The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio. To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.


News Article | May 1, 2017
Site: phys.org

Image generated by the glow stick probe of cancerous cells. Credit: Prof. Doron Shabat/American Friends of Tel Aviv University (AFTAU) Chemiluminescence, or chemical light, is the principle behind the glow sticks (also known as light sticks) used at rock concerts and as quick tools to grab when the electricity goes out. But they can also be used to diagnose diseases by identifying concentrations of biological samples. A new mechanism developed by Tel Aviv University researchers produces a 3,000-times-brighter, water-resistant chemiluminescent probe with particular application to medical and cancer diagnosis. The research found that tweaking the electronic structure of current probes improves their inherent fluorescence. This could lead to the invention of a new single-component system with multiple applications—including the detection and measurement of cellular activity that points to certain pathologies, such as cancer. The study was recently published in ACS Central Science. "Chemiluminescence is considered one of the most sensitive methods used in diagnostic testing," said Prof. Doron Shabat of TAU's School of Chemistry, who led the research. "We have developed a method to prepare highly efficient compounds that emit light upon contact with a specific protein or chemical. These compounds can be used as molecular probes to detect cancerous cells, among other applications." The research, conducted in collaboration with Dr. Christoph Bauer of Geneva University, repairs an energy-loss "glitch" in current chemiluminescent probes. Most systems use a mixture of one emitter molecule that detects the species of interest, and another two additional ingredients—a fluorophore and a soap-like substance called a surfactant—that amplify the signal to detectable levels. But energy is lost in the transfer process from the emitter molecule to the fluorophore, and surfactants are not biocompatible. "As synthetic chemists, we knew how to link structure and function," said Prof. Shabat. "By adding two key atoms, we created a much brighter probe than those currently on the market. In addition, this particular molecule is suitable for direct use in cells." Based on this molecule, the researchers developed sensors to detect several biologically relevant chemicals. They also used the chemiluminescent molecule to measure the activity of several enzymes and to image cells by microscopy. "This gives us a new powerful methodology with which we can prepare highly efficient chemiluminescence sensors for the detection, imaging and analysis of various cell activities," said Prof. Shabat. The researchers are currently exploring ways of amplifying the chemiluminescence of the new probes for in vivo imaging. More information: Ori Green et al, Opening a Gateway for Chemiluminescence Cell Imaging: Distinctive Methodology for Design of Bright Chemiluminescent Dioxetane Probes, ACS Central Science (2017). DOI: 10.1021/acscentsci.7b00058


News Article | February 22, 2017
Site: www.eurekalert.org

Chemists at the University of Waterloo, SCIEX and Pfizer have discovered a new way to help the pharmaceutical industry identify and test new drugs, which could revolutionize drug development, and substantially reduce the cost and time drugs need to reach their market. The study, published in the journal ACS Central Science, outlines a technique called differential mobility spectrometry (DMS) which analyzes drug molecules based on their response to an electrical field and the condensation-evaporation cycles the drug experiences in that field via a process, known as microsolvation. "We can use this technique to measure drug properties in seconds to minutes with only nanograms of sample," says Scott Hopkins, a professor of chemistry at the University of Waterloo and corresponding author on the paper. "It's cost saving and high throughput, so you can test hundreds, even thousands of drugs quickly, increasing the rate of drug discovery." Currently drug candidates are put through a battery of tests to measure their chemical and physical properties, such as how easily the drug crosses cell membranes, to predict how it will behave in the human body. Drugs must perform within a specific range in order to move forward to clinical trials. Most drugs fail the initial stages resulting in lost time and money. "It takes time to grow cells and run replicate experiments to measure permeability," said Hopkins. "These kinds of assays are an arduous process, and the people that conduct this work are artists as well as scientists." In contrast, these essential physical and chemical properties can be extracted all at once with a single analysis using DMS. The technique is so sensitive it can differentiate between the same drug molecules with slightly different atomic structures - something traditional testing methods cannot do. "With this technology, the initial stages of drug development testing can be completed in hours rather than days," says Hopkins. "It's not only several orders of magnitude faster, it gives us information we never had access to before that we can use for rational drug design." Beyond improving the testing and design drugs go through, Hopkins is hopeful this technology will improve the success of candidate drugs being proposed in the first place by informing the design process.


News Article | February 22, 2017
Site: phys.org

The study, published in the journal ACS Central Science, outlines a technique called differential mobility spectrometry (DMS) which analyzes drug molecules based on their response to an electrical field and the condensation-evaporation cycles the drug experiences in that field via a process, known as microsolvation. "We can use this technique to measure drug properties in seconds to minutes with only nanograms of sample," says Scott Hopkins, a professor of chemistry at the University of Waterloo and corresponding author on the paper. "It's cost saving and high throughput, so you can test hundreds, even thousands of drugs quickly, increasing the rate of drug discovery." Currently drug candidates are put through a battery of tests to measure their chemical and physical properties, such as how easily the drug crosses cell membranes, to predict how it will behave in the human body. Drugs must perform within a specific range in order to move forward to clinical trials. Most drugs fail the initial stages resulting in lost time and money. "It takes time to grow cells and run replicate experiments to measure permeability," said Hopkins. "These kinds of assays are an arduous process, and the people that conduct this work are artists as well as scientists." In contrast, these essential physical and chemical properties can be extracted all at once with a single analysis using DMS. The technique is so sensitive it can differentiate between the same drug molecules with slightly different atomic structures - something traditional testing methods cannot do. "With this technology, the initial stages of drug development testing can be completed in hours rather than days," says Hopkins. "It's not only several orders of magnitude faster, it gives us information we never had access to before that we can use for rational drug design." Beyond improving the testing and design drugs go through, Hopkins is hopeful this technology will improve the success of candidate drugs being proposed in the first place by informing the design process. Explore further: Researchers use light to control human heart cells and expedite development of new drugs


News Article | November 1, 2016
Site: www.sciencedaily.com

A team of researchers from the University of Minnesota and The Dow Chemical Company have discovered a new method for customizing ingredients that help oral medications dissolve in the body and be absorbed into the bloodstream. The materials discovered in this study could allow life-saving drugs to work faster and more efficiently. The University of Minnesota and Dow have filed a patent on the discovery that may also lower the cost to produce new medications. The research study is now online and is published in the current issue of the American Chemical Society's ACS Central Science, a leading journal in the chemical sciences. One of the biggest challenges for pharmaceutical companies when developing oral medications is to ensure that the body will fully absorb the drug molecules. Many therapeutic structures do not easily dissolve on the molecular level, which means they are less effective. In that case, the dose must be increased for patients, which may increase side effects. "A way to explain the differences in solubility of medicines is to think of how sugar easily dissolves in water and is rapidly absorbed by your digestive system, whereas sand doesn't dissolve in water and if swallowed, would pass right through the digestive system," said Theresa Reineke, a chemistry professor in the University of Minnesota's College of Science and Engineering and lead researcher on the study. Drug companies add substances, called excipients, to help the medicines dissolve in the stomach and intestinal fluid, but there have been few improvements in recent years to this decades-old technology. The process outlined in the study is a major breakthrough that revolutionizes the process of making drug structures more soluble in the body so that they are better absorbed. Funded by Dow, researchers examined two medications -- phenytoin, an anti-seizure drug, and nilutamide, a drug used to treat advanced-stage prostate cancer. The team used automated equipment at Dow to synthesize long-chain molecules. Their efficiency as excipients with these drugs were then tested with facilities at the University of Minnesota, including the Characterization Facility located in the University's College of Science and Engineering. One particular excipient discovered by this research allowed these insoluble drugs to fully dissolve in simulated intestinal fluid in a test tube. When they tested phenytoin with the new excipient in rat models, it promoted drug absorption three times better than the previous formulation. "While we were pleased with the results with these specific drugs, the most important thing is that we have developed a high throughput methodology for excipient development that could be used by many companies to create other life-saving medicines," Reineke said. "It takes about $1 billion dollars and 10 to 15 years for a pharmaceutical company to develop a new drug, but then they sometimes find marketable formulations are limited by solubility," said Steven Guillaudeu, a lead R&D manager at Dow and co-author of the study. "The methodology our team has created could help drug companies advance their pipeline compounds by using a better method to improve solubility and therefore bioavailability. The approach could have a major impact on the multibillion-dollar industry." The research discovery is one result of a five-year collaboration between Dow and the University of Minnesota for research partnerships to develop new chemical solutions, improve research facilities, and train the next generation of scientists. "This discovery is a perfect example of what can happen when industry and academia come together," said Frank Bates, a Regents Professor in the University's Department of Chemical Engineering and Materials Science and co-author of the study. "This research has yielded something that could have a huge effect on human health and lower the cost of medications."

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