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
Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Health and Medicine
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences