Researchers from the Universidad de Alcalá (UAH) managed by Professor Federico Gago from the pharmacology department, have published an article in the Journal of Medicinal Chemistry clarifying the molecular bases of DNA sequence identification by Thiocoraline A, a marine antibiotic compound with antitumoral action.
This molecule is a product of the biopharmaceutical company PharmaMar (http://www.pharmamar.com/es/pipeline/) and has a potent cytotoxic effect over a wide range of tumour cells both animal and human. The 3D structure of thiocoraline, determined by X-ray crystallography at the Universidad de Santiago de Compostela, shows a characteristic staple shaped pattern that explains its bisintercalative property in the DNA double helix (fig) as well as the particular arrangement of the pairs, piling up in columns inside the crystal structure.
Thanks to this double intercalation, thiocoraline is able to identify specific sequences of DNA and attaches to them, making it harder for the strands of DNA that form the double helix to separate.
In order to evaluate this effect, Professor Alberto Domingo from the biochemistry and molecular biology department of the UAH used tiny quantities of DNA linked to a fluorescent marker and standard instruments for reverse transcription polymerase chain reaction (RT-PCR). The information produced by this miniaturised method, that has proven to be a far superior technique to the those used in the past for this kind of experimentation, shows the binding affinity of thiocoraline for DNA in great detail, and has later been computer modelled for better understanding. In this way, it has been possible to verify that the flat rings of this molecule intertwine with the two closest base pairs while leaving another two pairs in between free in accordance with the exclusion principle; the rest of the molecule establishes hydrogen bonds with the central base pairs.
The resulting complex resembles a sandwich in which the bread is represented by the rings of the agent and the filling is the base pairs trapped by the thiocoraline (fig). It’s mainly these hydrogen bonds that grant the antibiotic the ability to bind selectively and this area is currently still under investigation at PharmaMar, a company of the Zeltia group that was recently granted approval by the Spanish health authorities for a new product of marine origin - the trabectedin (Yondelis) - aimed to treat sarcoma in soft tissues.
Authors: Federico Gago y Ana Negri
Oficina de Información Científic | alfa
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences