Nav: Home

'Metal' drugs to fight cancer

December 21, 2015

Pharmaceutical research can be difficult and frustrating. Often, one happens to synthesize a molecule without knowing exactly what kind of therapeutic effect it will have (if it ever will have any). "It is rare for someone to develop a new active drug already knowing what mechanism it will trigger in the body", explains Alessandra Magistrato, CNR-IOM/SISSA research scientist. "This also applies to the most widespread chemotherapeutic drugs, like cisplatin, or novel ones based on ruthenium". "Studies relying on modelling and simulations, like the ones we do here, may be very helpful in this sense, in that they increase our insights into the molecular mechanisms of action exerted by the drugs inside the body's cells", the scientist explains.

Magistrato is among the authors of a new study that reviews previously published experimental and computational reports visualized through the "lens" of computational microscope. "We produced models that enable us to rationalize the action of chemotherapeutic molecules on the body's cells", Magistrato explains. "For some types of drugs, we tried to understand which chemical form of the drug is most abundant when it enters the blood circulation and it reaches the cell ".

Scientists in fact use the term "prodrug" when referring to an injected chemotherapy agent; this, because as soon as the agent enters the body, it quickly changes before the interactions with it biological target. That's why it is difficult to know precisely which molecule (and how much of it) is responsible for the therapeutic action, in other words the actual medication.

On the other hand for other drugs with a known active form, Giulia Palermo, first author and researcher at the Swiss Federal Institute of Technology in Lausanne (EPFL), described how the the drug binds to different targets inside the cell. "A molecule can act on three fronts: on free DNA, on chromatin (the most common form of packed DNA in the nucleus) and on other proteins found in the cell", explains Palermo. Depending on which target is involved, the action of the drug can vary widely, as well as its side effects. "In fact, it is believed that when the drug exhibits cytotoxic effects, it may bound preferentially to the DNA, whereas when it has anti-metastatic effects, it may act on the proteins involved in motility or on protein/DNA complexes affecting gene regulation, for example".

"With the help of studies like this, experimentalists can improve the rational design of the new therapeutic molecules so as to obtain drugs that are more effective and with fewer side effects, a very important aspect as we know very well how physically demanding chemotherapy is for patients", concludes Magistrato.

The study is the result of an international collaboration between CNR-IOM/SISSA and the research groups led by Ursula Roethlisberger (professor of computational chemistry and biochemistry at EPFL), Paul Dyson, expert in organometallic and medicinal chemistry at EPFL, and Curt Davey, leader in crystallography of protein/DNA complexes at Nanyang Technological University (NTU) in Singapore.
-end-


International School of Advanced Studies (SISSA)

Related Dna Articles:

Penn State DNA ladders: Inexpensive molecular rulers for DNA research
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
It is easier for a DNA knot...
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
How do metals interact with DNA?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
Electrons use DNA like a wire for signaling DNA replication
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
Switched-on DNA
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Researchers are first to see DNA 'blink'
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
Finding our way around DNA
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
A 'strand' of DNA as never before
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
Doubling down on DNA
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
'Poring over' DNA
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.

Related Dna Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".