Promising candidates identified for COVID drugs

A team of researchers has identified several candidates for drugs against the coronavirus SARS-CoV-2 at DESY´s high-brilliance X-ray lightsource PETRA III. They bind to an important protein of the virus and could thus be the basis for a drug against Covid-19.

In a so-called X-ray screening, the researchers, under the leadership of DESY, tested almost 6000 known active substances that already exist for the treatment of other diseases in a short amount of time. After measuring about 7000 samples, the team was able to identify a total of 37 substances that bind to the main protease (Mpro) of the SARS-CoV-2 virus, as the scientists report online today in the journal Science. Seven of these substances inhibit the activity of the protein and thus slow down the multiplication of the virus. Two of them do this so promisingly that they are currently under further investigation in preclinical studies. This drug screening – probably the largest of its kind – also revealed a new binding site on the main protease of the virus to which drugs can couple.

Read more on the DESY website

Image: In the control hutch of the PETRA III beamline P11, DESY researcher Wiebke Ewert shows on a so-called electron density map where a drug candidate (green) binds to the main protease of the corona virus (blue).

Credit: DESY, Christian Schmid

The egg in the X-ray beam

Innovative time-resolved method reveals network formation by and dynamics of proteins.

A team of scientists has been using DESY’s X-ray source PETRA III to analyse the structural changes that take place in an egg when you cook it. The work reveals how the proteins in the white of a chicken egg unfold and cross-link with each other to form a solid structure when heated. Their innovative method can be of interest to the food industry as well as to the broad field of research surrounding protein analysis. The cooperation of two groups, headed by Frank Schreiber from the University of Tübingen and Christian Gutt from the University of Siegen, with scientists at DESY and European XFEL, reports the research in two articles in the journal Physical Review Letters.

Eggs are among the most versatile food ingredients. They can take the form of a gel or a foam, they can be comparatively solid and also serve as the basis for emulsions. At about 80 degrees Celsius, egg white becomes solid and opaque. This is because the proteins in the egg white form a network structure. Studying the exact molecular structure of egg white calls for energetic radiation, such as X-rays which is able to penetrate the opaque egg white and has a wavelength that is not longer than the structures being examined.

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Image: When heated, the proteins in the originally transparent chicken egg white form a tightly meshed, opaque network.

Credit: DESY, Gesine Born

Researchers watch nanomaterials growing in real time

For the first time, a team of scientists including from DESY has succeeded in capturing in real time the first few milliseconds in the life of a gold coating as it forms on a polymer. The team used PETRA III to observe the earliest stages in the growth of a metal-polymer hybrid material as a film of gold was applied to a polymer carrier, in a process that can be used in industrial applications. The group’s research, which it presented now in the journal Nanoscale Horizons, not only offers important new insights into how innovative hybrid nanomaterials form, it also sets a new world record in the temporal resolution achieved using GISAXS, a surface-sensitive scattering technique.

Metal-polymer materials form the basis of modern flexible electronics, such as organic field effect transistors (OFET) or novel television screens (OLED). A detailed understanding of the manufacturing process is essential in order to manufacture such composites using smaller amounts of starting materials, to make them more energy-efficient and to be able to use them more flexibly.

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Image: Experimental setup on beamline P03: The high-brilliance X-ray beam from PETRA III (magenta) is scattered by the surface structures while gold atoms are rapidly deposited on wafer-thin layers of plastic. The deflected X-ray light is recorded using a special high-speed camera designed at DESY. The sophisticated analysis of the real-time data obtained provides clues about the change in the sizes, distances and density profile of the resulting metal-polymer boundary layer

Credit: DESY/M. Schwartzkopf

High-pressure experiments provide insight into icy planets

Research team determines compression behaviour of water ice in unprecedented detail

An international team of scientists has been using X-rays to take a look inside distant ice planets. At the PETRA III Extreme Conditions Beamline, they investigated how water ice behaves at high pressure, under conditions corresponding to those inside the planet Neptune, for example. At pressures up to almost two million times atmospheric pressure at sea level on Earth, the researchers were able to observe in unparalleled detail how water ice behaves under compression. The team, led by Hauke Marquardt from the University of Oxford, is presenting its findings in the scientific journal Physical Review B.

Planetary ices – such as water ice (H2O), methane ice (CH4) and ammonia ice (NH3) – make up large parts of the ice giants in our solar system and are very likely to occur inside many exoplanets, which are planets outside our solar system. “However, the physical properties and phase diagrams of these compounds are not sufficiently known at the pressures and temperatures that prevail inside planets,” explains Marquardt. “Previous experimental studies using X-ray diffraction in a static diamond anvil cell have contributed a great deal to our understanding of ices at high pressure, but they have been unable to adequately answer numerous questions.”

Read more on the DESY website

Image : Ice at room temperature: A mixture of water ice and liquid water in a high-pressure cell at a temperature around 25 degrees Celsius and a pressure of one gigapascal, which corresponds to 10 000 times atmospheric pressure

Credit: DESY, Hanns-Peter Liermann

Minerals let Earth’s oceans seep down deeper than expected

Amphiboles could carry the volume of the Arctic Ocean into Earth’s mantle in 200 million years

A bigger volume of the world’s oceans is seeping deeper into Earth’s mantle than expected: That is the result of a study investigating a water-bearing mineral abundant in the oceanic crust. High-pressure experiments at DESY’s X-ray source PETRA III show that the mineral glaucophane is surprisingly stable up to 240 kilometres underground, which means it also carries water down to this depth. Scientists attribute this to the gradual cooling of Earth’s interior over geological timescales. The cooler temperatures let glaucophane and possibly other water-bearing minerals survive to greater pressures, as the team headed by Yongjae Lee from Yonsei University in South Korea reports in the journal Nature Communications. The scientists estimate that in about 200 million years, an additional volume equal to the Arctic Ocean could seep deep into Earth’s mantle this way.

Read more on the DESY website

Image: In the high-pressure cell, glaucophane samples are heated and squeezed between two diamond anvils

Credit: Yonsei University, Yoonah Bang/Huijeong Hwang

Quantum beats for zeptosecond timing

A team of scientists is developing high-precision timing for quantum technologies

Quantum systems will be crucial to future technologies. However, in order to use such systems in practical applications, it is necessary to control and manipulate them with great precision. A Hamburg research team has now succeeded in controlling and measuring a quantum system with hitherto unattainable temporal precision on the PETRA III beamline P01. They managed to control and detect oscillations inside an atomic nucleus, as well as the gamma radiation emitted, to within 1.3 zeptoseconds. A zeptosecond is 0.000 000 000 000 001 seconds; the thousandth part of a billionth of a billionth of a second. The new method developed by the team makes use of the fundamental excitations that occur within a solid. Precise adjustments of this kind are important when building quantum sensors, for example, to establish extremely precise time standards or to detect minute changes. The newly developed method may also have potential applications in quantum computers or quantum communication, as a way of making specific adjustments to such systems.

Read more on the DESY website

Image: View of the experiment at the PETRA III beamline P01 (in X-ray beam direction): The sample on the round table in the centre of the picture is connected to microwave measuring tips. The X-rays emitted by the sample are analysed at the end with a detector. Electromagnets with iron yokes around the sample table generate a magnetic field at the sample location to align the magnetisation in the sample

Credit: L. Bocklage/DESY

How deadly parasites ‘glide’ into human cells

X-ray analysis reveals structure of molecular machinery of malaria and toxoplasmosis pathogens

An investigation at DESY’s X-ray source PETRA III provides new insights into the molecular machinery by which certain parasites travel through the human organism. The study, led by Christian Löw from the Hamburg branch of the European Molecular Biology Laboratory EMBL, analyzed the so-called gliding movement of the malaria and toxoplasmosis parasites. The results, which the interdisciplinary team presents in the journal Communications Biology, can aid the search for new drugs against the pathogens.

In biological terms, gliding refers to the type of movement during which a cell moves along a surface without changing its shape. This form of movement is unique to parasites from the phylum Apicomplexa, such as Plasmodium and Toxoplasma. Both parasites, which are transmitted by mosquitoes and cats, have an enormous impact on global heath. Plasmodium causes 228 million malaria infections and around 400 000 deaths per year. Toxoplasma, which infects even one third of the human population, can cause severe symptoms in some people, and is particularly dangerous during pregnancy.

Read more on the DESY PETRA III website

Image: Molecular structure of essential light chain (ELC) protein in Plasmodium glideosome. Blue represents the electron density of the protein, with bonds between atoms indicated in yellow and water molecules indicated in red. The crystal structure at a resolution of 1.5 Ångström (0.15 millionths of a millimetre) was obtained at the EMBL beamlines at DESY’S X-ray source PETRA III. Credit: EMBL, Samuel Pazicky

Searching for the chemistry of life

Study shows possible new way to create DNA base pairs

In the search for the chemical origins of life, researchers have found a possible alternative path for the emergence of the characteristic DNA pattern: According to the experiments, the characteristic DNA base pairs can form by dry heating, without water or other solvents. The team led by Ivan Halasz from the Ruđer Bošković Institute and Ernest Meštrović from the pharmaceutical company Xellia presents its observations from DESY’s X-ray source PETRA III in the journal Chemical Communications.

“One of the most intriguing questions in the search for the origin of life is how the chemical selection occurred and how the first biomolecules formed,” says Tomislav Stolar from the Ruđer Bošković Institute in Zagreb, the first author on the paper. While living cells control the production of biomolecules with their sophisticated machinery, the first molecular and supramolecular building blocks of life were likely created by pure chemistry and without enzyme catalysis. For their study, the scientists investigated the formation of nucleobase pairs that act as molecular recognition units in the Deoxyribonucleic Acid (DNA).

Read more on the PETRA III (DESY) website

Image: From the mixture of all four nucleobases, A:T pairs emerged at about 100 degrees Celsius and G:C pairs formed at 200 degrees Celsius. Credit: Ruđer Bošković Institute, Ivan Halasz

High-pressure study advances understanding of promising battery materials

X-ray investigation shows systematic distortion of the crystal lattice of high-entropy oxides

In a high-pressure X-ray study, scientists have gained new insights into the characteristics of a promising new class of materials for batteries and other applications. The team led by Qiaoshi Zeng from the Center for High Pressure Science in China used the brilliant X-rays from DESY’s research light source PETRA III to analyse a so-called high-entropy oxide (HEO) under increasing pressure. The study, published in the journal Materials Today Advances is a first, but very important step paving a way for a broader picture and solid understanding of HEO materials.

Modern society requires industry to manufacture efficiently sustainable products for everyday life, for example batteries for smart phones. About five years ago, a new class of materials emerged that appears to be very promising for the design of new applications, especially batteries. These high-entropy oxides consist of at least five metals that are distributed randomly in a common simple crystal lattice, while their crystal structure can be different from each metal’s generic lattice. A popular example of a HEO material consists of 20 per cent each of cobalt, copper, magnesium, nickel and zinc for every oxygen atom, or (Co0.2Cu0.2Mg0.2Ni0.2Zn0.2)O.

Read more on the DESY website

Image: Example of a high-entropy oxide between the anvils of a diamond anvil cell used to exert increasing pressure on the sample. Credit: Center of High Pressure Science, Qiaoshi Zeng

Milling towards Green Chemistry

Real-time X-ray investigations reveal strong influence of milling equipment on mechanochemical reactions

The result of mechanochemical synthesis can be altered simply by selecting different milling jars and balls. Using the bright X-ray light from PETRA III (shown in green), the team was able to follow the formation of different polymorphs live. (Credit: McGill University, Luzia Germann)

The physical properties of milling jars and balls used in mechanically driven chemical reactions have a considerable influence on the reaction mechanism and outcome. Achieved at PETRA III, this is the result of a time-resolved X-ray study of mechanochemical syntheses. It shows that the material of milling jars, as well as the size and material of the milling balls can be specifically used to control the results of mechanochemical co-crystallisations, as Luzia S. Germann from McGill University (Canada) and co-workers report in the Royal Society of Chemistry’s journal Chemical Science.

Mechanochemistry has recently gained a lot of attention as a cornerstone of green and environmentally-friendly solvent-free synthetic methods. The results of the synchrotron X-ray powder diffraction experiments will contribute to a better understanding of mechanochemical processes and how they can be used in the future to explore the synthesis of new materials.

Read more on the DESY website

Image: The result of mechanochemical synthesis can be altered simply by selecting different milling jars and balls. Using the bright X-ray light from PETRA III (shown in green), the team was able to follow the formation of different polymorphs live. (Credit: McGill University, Luzia Germann)

Nanocrystals arrange themselves to form new lattices

Tiny structure that conducts electricity anisotropically offers foundation for new electronic components

Electronic components such as light-emitting diodes or solar cells can never be too minute. The smaller they are, the less power they consume and the wider the range of possible applications. In order to explore smaller and smaller worlds, scientists are constantly on the lookout for new materials with interesting properties. A research team from the University of Tübingen, working with colleagues at DESY and from Russia, has now made such a discovery.

Three-dimensional lattice of nanocrystals and semiconducting molecules. The precise arrangement of the nanocrystals allows current in the form of electrons (e-) to flow in certain directions. Illustration: University of Tübingen, Andre Maier.The scientists attached semiconducting organic molecules to inorganic nanocrystals to form ordered, three-dimensional lattices that have a uniform superstructure and are electrical conductors. “For the first time ever, we were able to determine a correlation between the conductivity and the direction of electrical transport in such lattices made up of nanocrystals,” said Marcus Scheele from the University of Tübingen, one of the team’s two leaders, adding that this is hugely significant in terms of their use in electronic components.

Read more on the DESY website

Image: Three-dimensional lattice of nanocrystals and semiconduction molecules. The prcise arrangement of the nanocrystals allows current in the form of electrons (e-) to flow in certain directions. Illustration: University of Tübingen, Andre Maier.

Unravelling the secrets of the malaria parasite

PETRA III helps to identify a new kind of protein in Plasmodium falciparum

For the first time, scientists have identified a lipocalin protein in the malaria parasite Plasmodium falciparum. The discovery helps to better understand the life cycle of the parasite that is a major health burden in large parts of the world. The cooperation between the groups of Tim Gilberger from the Centre for Structural Systems Biology CSSB (Cellular Parasitology Department at Bernhard Nocht Institute for Tropical Medicine/ Universität Hamburg) at DESY and Matthias Wilmanns from the Hamburg branch of the European Molecular Biology Laboratory EMBL describes the discovery in the journal Cell Reports. CSSB is a cooperation of nine institutions, including DESY, that have deputed scientists to the centre.

With an estimated 228 million cases per year worldwide and more than 400,000 deaths, malaria remains one of the most important human health threats. There is no vaccine commercially available. While biologists have revealed many details about how the malaria parasite rapidly feeds on and transforms its host’s red blood cells, there are many unsolved mysteries surrounding the parasite’s life cycle. Using the microscopic facilities available at CSSB in combination with EMBL’s X-ray beamlines at DESY’s research light source PETRA III, the team unraveled a small piece of this mystery with the identification and characterization of the first lipocalin in the most virulent malaria parasite species P. falciparum.

Read more on the PETRA III (at DESY) website

Image: Ribbon diagram of the protein structure of Plasmodium falciparum Lipocalin PfLCN that comes in tertramers, i.e. complexes of four identical molecules. Fluorescence micrographs of the parasite (upper right and lower left) show that the lipocalin accumulates in vacuoles.

Credit: BNITM/EMBL, Paul-Christian Burda/Thomas Crosskey [Source]

Scientists discover new forms of feldspars

High-pressure experiments reveal unknown variants of common mineral

In high-pressure experiments, scientists have discovered new forms of the common mineral feldspar. At moderate temperatures, these hitherto unknown variants are stable at pressures of Earth’s upper mantle, where common feldspar normally cannot exist. The discovery could change the view at cold subducting plates and the interpretation of seismologic signatures, as the team around DESY scientist Anna Pakhomova and Leonid Dubrovinsky from Bayerisches Geoinstitut in Bayreuth report in the journal Nature Communications.Feldspars represent a group of rock forming minerals that are highly abundant on Earth and make up roughly 60 per cent of Earth’s crust. The most common feldspars are anorthite, (CaSi2Al2O8), albite (NaAlSi3O8), and microcline (KAlSi3O8). At ambient conditions, the aluminium and silicon atoms in the crystal are each bonded to four oxygen atoms, forming AlOand SiO4 tetrahedra.

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Image : The crystal structure of the feldspar anorthite under normal conditions (left) and the newly discovered high-pressure variant (right). Under normal conditions, the silicon and aluminium atoms form tetrahedra (yellow and blue) with four oxygen atoms each (red). Under high pressure polyhedra with five and six oxygen atoms are formed. Calcium atoms (grey) lie in between. The black lines outline the so-called unit cell, the smallest unit of a crystal lattice. 

Credit : DESY, Anna Pakhomova

Plastic from Wood

X-ray analysis points the way to lignin-based components made to measure

The biopolymer lignin is a by-product of papermaking and a promising raw material for manufacturing sustainable plastic materials. However, the quality of this naturally occurring product is not as uniform as that of petroleum-based plastics. An X-ray analysis carried out at DESY reveals for the first time how the internal molecular structure of different lignin products is related to the macroscopic properties of the respective materials. The study, which has been published in the journal Applied Polymer Materials, provides an approach for a systematic understanding of lignin as a raw material to allow for production of lignin-based bioplastics with different properties, depending on the specific application.

Read more on the PETRA III at DESY website (opens in a new tab)”>>Read more on the PETRA III at DESY website

Image: Lignin is a promising raw material (left) for thermoplast (right) production.
Credit: KTH Stockholm, Marcus Jawerth

Double X-ray vision helps tuberculosis and osteoporosis research

Combination measurement shows distribution of metals in biological samples

With an advanced X-ray combination technique, scientists have traced nanocarriers for tuberculosis drugs within cells with very high precision. The method combines two sophisticated scanning X-ray measurements and can locate minute amounts of various metals in biological samples at very high resolution, as a team around DESY scientist Karolina Stachnik reports in the journal Scientific Reports. To illustrate its versatility, the researchers have also used the combination method to map the calcium content in human bone, an analysis that can benefit osteoporosis research.“Metals play key roles in numerous biological processes, from the oxygen transport in our red blood cells and the mineralisation of bones to the detrimental accumulation of metals in nerve cells as seen in diseases like Alzheimer’s,” explains Stachnik who works in the Center for Free-Electron Laser Science CFEL at DESY. High-energy X-rays make metals light up in fluorescence, a method that is very sensitive even to tiny amounts. “However, the X-ray fluorescence measurements usually do not show the ultrastructure of a cell, for example,” says DESY scientist Alke Meents who led the research. “If you want to exactly locate the metals within your sample, you have to combine the measurements with an imaging technique.” The ultrastructure comprises the details of the cell morphology that are not visible under an optical microscope.

>Read More on the DESY Website

Image: Two agglomerates of antibiotic-loaded iron nanocontainers (red) in a macrophage. Credit: Stachnik et al., „Scientific Reports“, CC BY 4.0

Tuneable self-organisation of liquid crystals in nanopores

Innovative path to novel materials with adaptive electrical and optical properties

A team of researchers has used X-rays from DESY’s research light source PETRA III to explore the amazingly diverse self-organisation of liquid crystals in nanometre-sized pores. The study, led by Patrick Huber from the Hamburg University of Technology (TUHH), shows how liquid crystals arrange themselves in pores of different sizes, exhibiting different electrical and optical properties. These could be of interest for applications such as sensors and novel optical metamaterials, as the group around first author Kathrin Sentker from TUHH reports in the journal Nanoscale. The research, which Huber presented at the annual DESY Users’ Meeting running until this Friday, will be continued within the framework of the planned Centre for Multiscale Materials Systems (CIMMS), in which TUHH, University of Hamburg, Helmholtz-Zentrum Geesthacht and DESY are involved and for which the Hamburg Science Authority has just approved approximately four million euros funding.

The researchers had studied a special liquid crystal material called HAT6 (2,3,6,7,10,11-hexakis(hexyloxy)triphenylene; C54H84O6), whose single molecules are disc-shaped. Below about 70 degrees Celsius, they arrange themselves into a liquid crystal; by heating to about 100 degrees, the order can be broken. The scientists filled this material into pores in an aluminium oxide substrate and cooled it down. The cylindrical pores were 17 to 160 nanometres (millionths of a millimeter) in diameter, 0.1 millimetres long and situated on a regular, hexagonal lattice.

Read more on the PETRA III website

Image: Simulation of the different orders of the liquid crystal, matching the measurements. Simulation: Marco D. Mazza, Max Planck Institute for dynamics and self-organisation and und Loughborough University