Pocket chemistry: DNA helps glucose meters measure more than sugar

Glucose meters aren't just for diabetics anymore. Thanks to University of Illinois chemists, they can be used as simple, portable, inexpensive meters for a number of target molecules in blood, serum, water or food.

Chemistry professor Yi Lu and postdoctoral researcher Yu Xiang published their findings in the journal Nature Chemistry.

"The advantages of our method are high portability, low cost, wide availability and quantitative detection of a broad range of targets in medical diagnostics and environmental monitoring," Lu said. "Anyone could use it for a wide range of detections at home and in the field for targets they may care about, such as vital metabolites for a healthy living, contaminants in their drinking water or food, or potential disease markers."

A glucose meter is one of the few widely available devices that can quantitatively detect target molecules in a solution, a necessity for diagnosis and detection, but only responds to one chemical: glucose. To use them to detect another target, the researchers coupled them with a class of molecular sensors called functional DNA sensors.

Functional DNA sensors use short segments of DNA that bind to specific targets. A number of functional DNAs and RNAs are available to recognize a wide variety of targets.

They have been used in the laboratory in conjunction with complex and more expensive equipment, but Lu and Xiang saw the potential for partnering them with pocket glucose meters.

The DNA segments, immobilized on magnetic particles, are bound to the enzyme invertase, which can catalyze conversion of sucrose (table sugar) to glucose. The user adds a sample of blood, serum or water to the functional DNA sensor to test for drugs, disease markers, contaminants or other molecules. When the target molecule binds to the DNA, invertase is released into the solution. After removing the magnetic particle by a magnet, the glucose level of the sample rises in proportion to the amount of invertase released, so the user then can employ a glucose meter to quantify the target molecule in the original sample.

"Our method significantly expands the range of targets the glucose monitor can detect," said Lu, who also is affiliated with the Beckman Institute for Advanced Science and Technology and with the Frederick Seitz Materials Research Lab at U. of I. "It is simple enough for someone to use at home, without the high costs and long waiting period of going to the clinics or sending samples to professional labs."

The researchers demonstrated using functional DNA with glucose meters to detect cocaine, the disease marker interferon, adenosine and uranium. The two-step method could be used to detect any kind of molecule that a functional DNA or RNA can bind.

Next, the researchers plan to further simplify their method, which now requires users to first apply the sample to the functional DNA sensor and then to the glucose meter.

"We are working on integrating the procedures into one step to make it even simpler," Lu said. "Our technology is new and, given time, it will be developed into an even more user-friendly format."

Provided by University of Illinois at Urbana-Champaign (news : web)

Pocket chemistry: DNA helps glucose meters measure more than sugar

 Glucose meters aren't just for diabetics anymore. Thanks to University of Illinois chemists, they can be used as simple, portable, inexpensive meters for a number of target molecules in blood, serum, water or food.

Chemistry professor Yi Lu and postdoctoral researcher Yu Xiang published their findings in the journal Nature Chemistry.

"The advantages of our method are high portability, low cost, wide availability and quantitative detection of a broad range of targets in medical diagnostics and environmental monitoring," Lu said. "Anyone could use it for a wide range of detections at home and in the field for targets they may care about, such as vital metabolites for a healthy living, contaminants in their drinking water or food, or potential disease markers."

A glucose meter is one of the few widely available devices that can quantitatively detect target molecules in a solution, a necessity for diagnosis and detection, but only responds to one chemical: glucose. To use them to detect another target, the researchers coupled them with a class of molecular sensors called functional DNA sensors.

Functional DNA sensors use short segments of DNA that bind to specific targets. A number of functional DNAs and RNAs are available to recognize a wide variety of targets.

They have been used in the laboratory in conjunction with complex and more expensive equipment, but Lu and Xiang saw the potential for partnering them with pocket glucose meters.

The DNA segments, immobilized on magnetic particles, are bound to the enzyme invertase, which can catalyze conversion of sucrose (table sugar) to glucose. The user adds a sample of blood, serum or water to the functional DNA sensor to test for drugs, disease markers, contaminants or other molecules. When the target molecule binds to the DNA, invertase is released into the solution. After removing the magnetic particle by a magnet, the glucose level of the sample rises in proportion to the amount of invertase released, so the user then can employ a glucose meter to quantify the target molecule in the original sample.

"Our method significantly expands the range of targets the glucose monitor can detect," said Lu, who also is affiliated with the Beckman Institute for Advanced Science and Technology and with the Frederick Seitz Materials Research Lab at U. of I. "It is simple enough for someone to use at home, without the high costs and long waiting period of going to the clinics or sending samples to professional labs."

The researchers demonstrated using functional DNA with glucose meters to detect cocaine, the disease marker interferon, adenosine and uranium. The two-step method could be used to detect any kind of molecule that a functional DNA or RNA can bind.

Next, the researchers plan to further simplify their method, which now requires users to first apply the sample to the functional DNA sensor and then to the glucose meter.

"We are working on integrating the procedures into one step to make it even simpler," Lu said. "Our technology is new and, given time, it will be developed into an even more user-friendly format."

The U.S. Department of Energy, the National Institutes of Health and the National Science Foundation supported this work.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Illinois at Urbana-Champaign, via EurekAlert!, a service of AAAS.

Journal Reference:

Yu Xiang, Yi Lu. Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets. Nature Chemistry, 2011; DOI: 10.1038/nchem.1092

Tuned enzymes: Extra guest molecule in an enzyme's binding pocket enables methane oxidation

 Our fossil fuel reserves are limited. When they run out, we will not only be lacking in fuel, but chemical industry will lose its most important feedstock. In contrast, natural gas has barely been used as a raw material. If it were possible to efficiently convert methane, the main component of natural gas, into chemically useful materials like methanol, we would gain some time to make the transition to alternative sources of raw materials.

In the journal Angewandte Chemie, Manfred T. Reetz and a team at the Max Planck Institute for Carbon Research in Mülheim (Germany) have now introduced a new approach for the enzymatic production of methanol from methane. Their secret is the inclusion of an inert guest in the enzyme’s binding pocket in order to make it smaller so that it can effectively bind methane.

Methanol is a useful starting material for many chemical syntheses, and it can also be added to conventional fuels to drive fuel cells. Conventional processes for producing methanol from methane involve detours (synthesis gas), are markedly complex and energy intensive, and require high temperatures and pressures. Nature, on the other hand, has a much more elegant route: the enzyme methane monooxygenase does the job gently and efficiently. Unfortunately this is a very complex enzyme that cannot easily be produced and used in an artificial environment. The cytochrome P450 (CYP) family of enzymes could represent an alternative starting point. The main job of these enzymes is the oxidation of various substances produced by the body or introduced to it. In the reaction, carbon–hydrogen bonds are oxidized to make alcohol groups (–OH). The active component of these enzymes is a heme, an iron–porphyrin complex similar to that in our hemoglobin.

The problem is that the binding pocket of this enzyme is just too big to snugly bind and oxidize small molecules such as methane. Instead of trying to devise complex methods to create a suitable enzyme, Reetz and his co-workers came up with a clever trick: chemically “tuning” a CYP enzyme. The scientists added an additional guest into the binding pocket in order to make it smaller.

The natural substrates for CYP enzymes are fatty acids. As a guest molecule, the researchers chose a compound that resembles a fatty acid, a carbonic acid in which all of the hydrogen atoms in the hydrocarbon chain have been replaced with fluorine atoms. This type of molecule is as water-repellent as the original, but takes up more room. The fluorine atoms make it chemically inert so that it does not participate in any reactions. Like the molecule it is modeled on, this guest is able to bring the iron–heme complex of the enzyme into its catalytically active state (high-spin state). The significantly smaller binding pocket now allows methane to bind effectively so that it can be oxidized to methanol.

Says Reetz: “The road to success is still far for a technical implementation, yet, the concept opens up new perspectives for the development of further reactions, such as the oxidation of other chemical compounds.”

More information: Manfred T. Reetz, Tuning a P450 Enzyme for Methane Oxidation, Angewandte Chemie International Edition, http://dx.doi.org/ … ie.201006587