Rice scientists reengineer cancer drugs to be more versatile

Rice University scientists have enlisted widely used cancer therapy systems to control gene expression in mammalian cells, a feat of synthetic biology that could change how diseases are treated.
Photo Credit: Jeff Fitlow/Rice University

Rice University scientists have enlisted widely used cancer therapy systems to control gene expression in mammalian cells, a feat of synthetic biology that could change how diseases are treated.

The lab of chemical and biomolecular engineer Xue Sherry Gao discovered a way to further tap the therapeutic potential of proteolysis targeting chimeras (PROTACs), small molecules that are used as effective tools for treating cancer, immune disorders, viral infections and neurodegenerative diseases.

Gao and collaborators reengineered the PROTAC molecular infrastructure and showed it can be used to achieve chemically induced dimerization (CID), a mechanism by which two proteins bind together only in the presence of a specific third molecule known as an inducer. The research is described in a study published in the Journal of the American Chemical Society.

‘Magic’ solvent creates stronger thin films

This micrograph image shows an initiated chemical vapor deposition coating made by doctoral student Pengyu Chen in the lab of Rong Yang, assistant professor in the Smith School of Chemical and Biomolecular Engineering in Cornell Engineering.
Image Credit: Courtesy of the researchers 

A new all-dry polymerization technique uses reactive vapors to create thin films with enhanced properties, such as mechanical strength, kinetics and morphology. The synthesis process is gentler on the environment than traditional high-temperature or solution-based manufacturing and could lead to improved polymer coatings for microelectronics, advanced batteries and therapeutics.

“This scalable technique of initiated chemical vapor deposition polymerization allows us to make new materials, without redesigning or revamping the whole chemistry. We just simply add an ‘active’ solvent,” said Rong Yang, assistant professor in the Smith School of Chemical and Biomolecular Engineering in Cornell Engineering. “It’s a little bit like a Lego. You team up with a new connecting piece. There’s a ton you can build now that you couldn’t do before.”

Yang collaborated on the project with Jingjie Yeo, assistant professor in the Sibley School of Mechanical and Aerospace Engineering, and Shefford Baker, associate professor of materials science and engineering.

How protein-rich droplets form

Martina Havenith-Newen has gained new insights by combining two methods.
Photo Credit: © RUB, Marquard

Terahertz spectroscopy can be used to explain the spontaneous formation of protein-rich droplets, which may lead to neurodegenerative diseases.

With the help of a new method, terahertz calometry, it is a research team of the Bochum Cluster of Excellence Ruhr Explores Solvation RESOLV succeeded in re-examining the spontaneous phase separation into a protein-rich and a low-protein phase in one solution. It is believed that the protein-rich droplets favor the formation of neurotoxic protein aggregates - a starting point for neurodegenerative diseases. The researchers around Prof. Dr. Martina Havenith, holder of the Chair for Physical Chemistry II at the Ruhr University Bochum, reports in the Journal of Physical Chemistry Letters from 6. February 2023.

Molecular level and time resolution in the picosecond range

The study is based on the work in the Terahertz-Calorimetry project, which was funded by the European Research Council with an Advanced Grant. "The visionary idea in the project was to marry two powerful techniques in physical chemistry - laser spectroscopy and calorimetry -" explains Grantee Martina Havenith.

Chemists Optimized Ceramic Material for Hydrogen Energy

The Institute of Hydrogen Energy is creating materials and technologies.
Photo Credit: Anna Popova

The team of scientists from the Institute of High-Temperature Electrochemistry, Ural Branch of the Russian Academy of Sciences, and the Ural Federal University has obtained a ceramic material for hydrogen energy. Chemists managed to synthesize, study, and improve the properties of layered barium stannate. This material can be used in fuel cells and electrolyzers. They are used to produce hydrogen or electrical energy. The scientists described the synthesis process and chemical properties of the material in an article in the Journal of Alloys and Compounds. 

"We have been investigating barium stannate, an understudied layered material, for use in high-temperature devices. We prepared samples and found that it begins to partially decompose into oxides when stored outdoors for long periods of time. We were able to improve the stability by adding lanthanum, but we did not completely eliminate the problem. However, since the material as a whole has quite good electron-conducting properties, it can certainly be used for applications as long as its contact with air is excluded. For example, lithium-containing components in lithium-ion batteries are also used in isolation because they ignite in contact with air," explains study co-author Dmitry Medvedev, head of the Hydrogen Energy Laboratory at the Ural Federal University.

Harmful Effects of Long-Term Alcohol Use Documented in Blood Protein Snapshot

Jon Jacobs recently found that a particular combination of blood proteins indicates alcohol-associated hepatitis, a deadly liver disease. 
Photo Credit: Eddie Pablo III | Pacific Northwest National Laboratory

Biochemist Jon Jacobs has analyzed the blood of patients with diseases and conditions such as Ebola, cancer, tuberculosis, hepatitis, diabetes, Lyme disease, brain injury and influenza.

But never has he seen blood chemistry gone so awry as when he and colleagues took an in-depth look at the protein activity in the blood of patients with alcohol-associated hepatitis, a severe form of liver disease caused by heavy drinking for many years.

“The proteins in these patients are more dysregulated than in any other blood plasma that we’ve analyzed,” said Jacobs, a scientist at the Department of Energy’s Pacific Northwest National Laboratory. “Almost two-thirds of the proteins we measured are at unusual levels. This is a snapshot of what’s going on in the body of a person with this disease and reflects just how severe a disease this is.”

That “snapshot” is a measurement of proteins that change in patients with the disease. The unique combination of changes in protein activity marks an important step toward development of a simple blood test to diagnose alcohol-associated hepatitis.

Jacobs and colleagues, including scientists and physicians from the Veteran Affairs Long Beach Healthcare System and the University of Pittsburgh, published their findings recently in the American Journal of Pathology. Corresponding authors of the study are Jacobs and Timothy Morgan, a gastroenterologist at VA Long Beach who has treated patients with the disease for more than 35 years.

Can clay capture carbon dioxide?

Sandia National Laboratories bioengineer Susan Rempe, left, and chemical engineer Tuan Ho peer through an artistic representation of the chemical structure of a kind of clay. Their team is studying how clay could be used to capture carbon dioxide.
Photo Credit: Craig Fritz

The atmospheric level of carbon dioxide — a gas that is great at trapping heat, contributing to climate change — is almost double what it was prior to the Industrial Revolution, yet it only constitutes 0.0415% of the air we breathe.

This presents a challenge to researchers attempting to design artificial trees or other methods of capturing carbon dioxide directly from the air. That challenge is one a Sandia National Laboratories-led team of scientists is attempting to solve.

Led by Sandia chemical engineer Tuan Ho, the team has been using powerful computer models combined with laboratory experiments to study how a kind of clay can soak up carbon dioxide and store it.

The scientists shared their initial findings in a paper published earlier this week in The Journal of Physical Chemistry Letters.

“These fundamental findings have potential for direct-air capture; that is what we’re working toward,” said Ho, lead author on the paper. “Clay is really inexpensive and abundant in nature. That should allow us to reduce the cost of direct-air carbon capture significantly, if this high-risk, high-reward project ultimately leads to a technology.”

"Snapshots" of Translation Could Help Us Investigate Cellular Proteins

Nascent polypeptide chains or polypeptidyl-tRNAs (pep-tRNAs) occur transiently during protein synthesis. The potential to study these intermediates and better understand their role in processes like gene regulation has been greatly enhanced by the development of a process termed PETEOS—short for peptidyl-tRNA enrichment using organic extraction and silica adsorption. This method, developed by scientists at Tokyo Tech, allows for the large-scale harvesting, processing, and identification of pep-tRNA polypeptide moieties.

Advances in molecular biology have revealed that pep-tRNAs—nascent polypeptides inside the ribosome that are covalently attached to transfer RNA—are involved in a myriad of cell functions, including gene expression. All proteins exist as pep-tRNAs at some point and studying these translation intermediates is vital as they possess properties of both RNA and protein and can help researchers better understand the specifics of translation. Depending on stimuli and/or stresses, translational regulation is very rapid and spans initiation, elongation, and elongation pausing. Garnering deeper insights into the process of translation therefore requires a suitable method to process pep-tRNAs in large quantities. These nuances have fueled the development of molecular tools to investigate cellular translation.

Making molecules faster

Replica of the complex molecule, stemoamide, built in mere three steps in Tim Cernak’s Lab.
Photo Credit: Austin Thomason, Michigan Photography

With a big assist from artificial intelligence and a heavy dose of human touch, Tim Cernak’s lab at the University of Michigan made a discovery that dramatically speeds up the time-consuming chemical process of building molecules that will be tomorrow’s medicines, agrichemicals or materials.

The discovery, published in the journal of Science, is the culmination of years of chemical synthesis and data science research by the Cernak Lab in the College of Pharmacy and Department of Chemistry.

The goal of the research was to identify key reactions in the synthesis of a molecule, ultimately reducing the process to as few steps as possible. In the end, Cernak and his team achieved the synthesis of a complex alkaloid found in nature in just three steps. Previous syntheses took between seven and 26 steps.

‘Game-changing’ findings for sustainable hydrogen production

Illustration Credit: Courtesy of University of Surrey

Hydrogen fuel could be a more viable alternative to traditional fossil fuels, according to University of Surrey researchers who have found that a type of metal-free catalysts could contribute to the development of cost-effective and sustainable hydrogen production technologies. 

The study has shown promising results for the use of edge-decorated nano carbons as metal-free catalysts for the direct conversion of methane, which is also a powerful greenhouse gas, into hydrogen. Among the nano carbons investigated, nitrogen-doped nano carbons presented the highest level of performance for hydrogen production at high temperatures. 

Crucially, the researchers also found that the nitrogen-doped and phosphorous-doped nano carbons had strong resistance to carbon poisoning, which is a common issue with catalysts in this process. 

Robots and A.I. team up to discover highly selective catalysts

Close up of the semi-automated synthesis robot used to generate training data
Photo Credit: ICReDD

Researchers used a chemical synthesis robot and computationally cost effective A.I. model to successfully predict and validate highly selective catalysts.

Artificial intelligence (A.I.) has made headlines recently with the advent of ChatGPT’s language processing capabilities. Creating a similarly powerful tool for chemical reaction design remains a significant challenge, especially for complex catalytic reactions. To help address this challenge, researchers at the Institute for Chemical Reaction Design and Discovery and the Max Planck Institut für Kohlenforschung have demonstrated a machine learning method that utilizes advanced yet efficient 2D chemical descriptors to accurately predict highly selective asymmetric catalysts—without the need for quantum chemical computations.  

“There have been several advanced technologies which can “predict” catalyst structures, but those methods often required large investments of calculation resources and time; yet their accuracy was still limited,” said joint first author Nobuya Tsuji. “In this project, we have developed a predictive model which you can run even with an everyday laptop PC.”

Molecular machines could treat fungal infections

Schematic representation of the mechanisms by which light-activated molecular machines kill fungi. Molecular machines bind to fungal mitochondria, decreasing adenosine triphosphate (ATP) production and impairing the function of energy-dependent transporters that control the movement of ions, such as calcium. This leads to the influx of water, which causes the organelles to swell and eventually the cells to burst.
Image Credit: Tour Group/Rice University

That stubborn athlete’s foot infection an estimated 70% of people get at some point in their life could become much easier to get rid of thanks to nanoscale drills activated by visible light.

Proven effective against antibiotic-resistant infectious bacteria and cancer cells, the molecular machines developed by Rice University chemist James Tour and collaborators are just as good at combating infectious fungi, according to a new study published in Advanced Science.

Based on the work of Nobel laureate Bernard Feringa, the Tour group’s molecular machines are nanoscale compounds whose paddlelike chain of atoms moves in a single direction when exposed to visible light. This causes a drilling motion that allows the machines to bore into the surface of cells, killing them.

Reading out RNA structures in real time

The fluorescent blinking of cyanine dye (Alexa Fluor 647, pink star) bound to RNA changes depending on the structure of the RNA. When the RNA is folded like a hairpin, the fluorescent blinking is fast, and when the RNA switches to a G-quadruplex, the blinking is slow
Illustration Credit: Akira Kitamura

A new microscopic technique allows for the real-time study of RNA G-quadruplexes in living cells, with implications for the fight against amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease and Stephen Hawking’s disease, is a neurodegenerative disease that results in the gradual loss of control over the muscles in the body. It is currently incurable and the cause of the disease is unknown in over 90% of all cases — although both genetic and environmental factors are believed to be involved.

The research groups of Dr. Akira Kitamura at the Faculty of Advanced Life Science, Hokkaido University, and Prof. Jerker Widengren at the KTH Royal Institute of Technology, Sweden, have developed a novel technique that is able to detect a characteristic structure of RNA in real time in live cells. The technique, which is based on fluorescence-microscopic spectroscopy, was published in the journal Nucleic Acids Research.

Solid material that 'upconverts' visible light photons to UV light photons could change how we utilize sunlight

Low-intensity visible blue light or lower energy photons being converted into higher energy UV photons using a solid film formed on a round glass substrate, developed by researchers at Tokyo Tech
 Image Credit: Prof. Yoichi Murakami

Ultraviolet (UV) light has higher energy photons than visible light and, thus, has more applications. Tokyo Tech researchers have now developed a brilliant innovation—a solid-state material that can stably and efficiently upconvert sunlight- intensity visible light photons to UV light photons. This photon upconversion (UC) material can utilize visible light to successfully drive reactions that would conventionally need UV light, broadening the spectrum of utility for the former.

The importance of solar power as a renewable energy resource is increasing. Sunlight contains high-energy UV light with a wavelength shorter than 400 nm, which can be broadly used, for example, for photopolymerization to form a resin and activation of photocatalysts to drive reactions that generate green hydrogen or useful hydrocarbons (fuels, sugars, olefins, etc.). The latter of these is often called "artificial photosynthesis." Photocatalytic reaction by UV light to efficiently kill viruses and bacteria is another important application. Unfortunately, only about 4% of terrestrial sunlight falls within the UV range in the electromagnetic spectrum. This leaves a large portion of sunlight spectrum unexploited for these purposes.

RUDN University Chemists Create Substances for Supramolecules Self-assembly

Illustration Credit: RUDN University

RUDN University chemists derived molecules that can assemble into complex structures using chlorine and bromine halogen atoms. They bind to each other as “Velcro” — chlorine “sticks” to bromine, and vice versa. As a result, supramolecules are assembled from individual molecules. The obtained substances will help to create supramolecules with catalytic, luminescent, conducting properties.

Supramolecules are the structures made of several molecules. Individual molecules are combined, for example, by self-assembly or without external control. The resulting structure has properties that the molecules did not have individually. That is the way to create new materials, catalysts, molecular machines for drug delivery, conductors, and so on. To get a material with the specified properties, you need to choose the right starting molecules and auxiliary substances that will ensure their unification. One of the ways to control self-assembly is halogen-halogen interactions. These are the chemical bonds forming between two halogens (for example, chlorine, fluorine, bromine). RUDN University chemists have created a molecule with a halogen bond that can form supramolecules by itself or provide the required self-assembly with other substances. They will help to create substances for the chemical industry, medicine, and electronics.

Targeting cancer with a multidrug nanoparticle

MIT chemists designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled.
Illustration Credit: Courtesy of the researchers. Edited by MIT News.

Treating cancer with combinations of drugs can be more effective than using a single drug. However, figuring out the optimal combination of drugs, and making sure that all of the drugs reach the right place, can be challenging.

To help address those challenges, MIT chemists have designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled. Using these particles, the researchers were able to calculate and then deliver the optimal ratio of three cancer drugs used to treat multiple myeloma.

“There’s a lot of interest in finding synergistic combination therapies for cancer, meaning that they leverage some underlying mechanism of the cancer cell that allows them to kill more effectively, but oftentimes we don’t know what that right ratio will be,” says Jeremiah Johnson, an MIT professor of chemistry and one of the senior authors of the study.

Mimicking an Enigmatic Property of Circadian Rhythms through an Artificial Chemical Clock

An innovative temperature-compensation mechanism for oscillating chemical reactions based on temperature-responsive gels has been recently reported by researchers at Tokyo Tech. Their experimental findings, alongside a detailed mathematical analysis, hint at the possibility that circadian rhythms found in nature may all rely on a similar mechanism, allowing their period to remain independent of temperature.

Circadian rhythms are natural, internal oscillations that synchronize an organism's behaviors and physiological processes with their environment. These rhythms normally have a period of 24 hours and are regulated by internal chemical clocks that respond to cues from outside the body, such as light.

Although well studied in animals, plants, and bacteria, circadian rhythms all share an enigmatic property—the oscillation period is not significantly affected by temperature, even though the rate of most biochemical reactions changes exponentially with temperature. This clearly indicates that some sort of temperature-compensation mechanism is at play. Interestingly, some scientists have managed to replicate such temperature-invariant qualities in certain oscillating chemical reactions. However, these reactions are often troublesome and require extremely precise adjustments on the reacting chemicals.

Artificial photosynthesis uses sunlight to make biodegradable plastic

Fumaric acid synthesis from CO2 using solar energy. Using sunlight to power the photoredox system pyruvic acid and CO2 are converted into fumaric acid, by malate dehydrogenase and fumarase.
Illustration Credit: Yutaka Amao, Osaka Metropolitan University

In recent years, environmental problems caused by global warming have become more apparent due to greenhouse gases such as CO2. In natural photosynthesis, CO2 is not reduced directly, but is bound to organic compounds which are converted to glucose or starch. Mimicking this, artificial photosynthesis could reduce CO2 by combining it into organic compounds to be used as raw materials, which can be converted into durable forms such as plastic.

A research team led by Professor Yutaka Amao from the Research Center for Artificial Photosynthesis and graduate student Mika Takeuchi, from the Osaka Metropolitan University Graduate School of Science, have succeeded in synthesizing fumaric acid from CO2, a raw material for plastics, powered—for the first time—by sunlight. Their findings were published in Sustainable Energy & Fuels.

New enzyme could mean better drugs

A scientist works in the lab of Rice’s Xue Sherry Gao.
Photo Credit: Jeff Fitlow/Rice University

Just as a choreographer’s notation tells a dancer to strike a particular pose, an enzyme newly discovered by Rice University scientists is able to tell specific molecules precisely how to arrange themselves, down to the angle of single hydrogen bonds.

Biomolecular engineers at Rice identified a new Diels-Alderase (DAase), an enzyme that catalyzes the Diels-Alder reaction, a widely used method of synthesizing important materials and pharmaceuticals, from raw materials for plastics and fuels to synthetic steroids.

The enzyme, known as CtdP, was previously thought to be a different type of protein — a “regulator” controlling gene expression. Regulators typically do not serve a catalytic function, meaning they cannot “transform compound A into compound B,” said study co-author Xue Sherry Gao.

Mirror Image: FSU study lays out chirality flipping theory

Ken Hanson, left, and Eugene DePrince, right, are faculty members in the Department of Chemistry and Biochemistry.
Photo Credit: Florida State University

Chemists can make a career out of controlling whether certain molecules are generated as a lefty or a righty.

Molecules don’t literally have hands, but scientists often refer to them in this way when looking at molecules that are mirror images of each other and therefore are not superimposable. And whether a molecule is a lefty or a righty directly affects how they behave and their use in everything from drug design to flavoring foods.

A Florida State University research team led by Associate Professor of Chemistry Ken Hanson previously found a way to turn “left-handed” molecules into “right-handed” ones by using light to induce a proton transfer and the transformation into a different isomer. Now, Hanson and his fellow FSU Professor of Chemistry Eugene DePrince are harnessing the power of math and computers to predict what would happen if you performed that same process in a gap between closely spaced mirrors.

Scientists Unveil Least Costly Carbon Capture System to Date

Chemist Dave Heldebrant, a recently selected fellow of the American Chemical Society who holds a joint appointment with Washington State University, has helped design several solvents that can deftly capture carbon dioxide molecules before they reach Earth’s atmosphere. 
Photo Credit: Andrea Starr | Pacific Northwest National Laboratory

The need for technology that can capture, remove and repurpose carbon dioxide grows stronger with every CO2 molecule that reaches Earth’s atmosphere. To meet that need, scientists at the Department of Energy’s Pacific Northwest National Laboratory have cleared a new milestone in their efforts to make carbon capture more affordable and widespread. They have created a new system that efficiently captures CO2—the least costly to date—and converts it into one of the world’s most widely used chemicals: methanol.

Snaring CO2 before it floats into the atmosphere is a key component in slowing global warming. Creating incentives for the largest emitters to adopt carbon capture technology, however, is an important precursor. The high cost of commercial capture technology is a longstanding barrier to its widespread use.

PNNL scientists believe methanol can provide that incentive. It has many uses as a fuel, solvent, and an important ingredient in plastics, paint, construction materials and car parts. Converting CO2 into useful substances like methanol offers a path for industrial entities to capture and repurpose their carbon.