Alchemists of the cell environment

(Nanowerk News) To analyse, understand, interfere, and correct. Researching about life machinery goes through deciphering how cells, the smaller alive units within an organism, work. Being healthy depends mainly in an adequate behaviour of our cells. In fact, nowadays it is well stablished that many diseases (such as cancer) start when malfunctioning is occurring inside them.
Thus, to diagnose and treat those diseases is strictly necessary to puzzle out the molecular keys that drive the cellular machinery, developing tools and technologies that allow us to alter the cellular behaviour in a controlled and predictable manner.
This is one of the main objectives of Prof. J. L. Mascareñas research group at CIQUS. In fact, one of their research lines involves the design of metal-based chemical catalysts that can be used as enzymes right after internalization in the living cell (enzymes are those proteins capable to accelerate most of the processes occurring at the body tissues).
In other words, to create artificial enzymes that will promote reactions which are not taking place spontaneously in living organisms.
Right to left: María Tomás, Cristian Vidal and Paolo Destito authors of this research work, together with Fernando López and Jose L. Mascareñas
Right to left: María Tomás, Cristian Vidal and Paolo Destito authors of this research work, together with Fernando López and Jose L. Mascareñas (Photo: Andrés Ruiz / CiQUS
This work is part of the METBIOCAT European Project, led by Prof. Mascareñas and funded by an Advanced Grant from the European Research Council (ERC). Previously, Mascareñas research group has shown the possibility of using Ruthenium-based catalysts to promote chemical transformations in vivo, also controlling chemical reactions at will in specific cell organelles, such as the mithocondria.
At the moment, CIQUS scientists communicate to the distinguished publication Nature Communications ("Concurrent and orthogonal gold(I) and ruthenium(II) catalysis inside living cells") a new type of chemical transformations promoted by gold catalysts, which increases the chances to get new bioactive compounds within the living cell in a fully controlled manner. And that, because in this case chemical reactions are just taking place when this brand-new catalyst is at play.

Suitable catalysts

This work was completely developed at the CIQUS laboratories by the following research group: the postdoctoral researcher Cristian Vidal, the 'Juan de la Cierva' fellow María Tomás, the PhD student Paolo Destito, and the CSIC tenure scientist Fernando López, under the supervision of Prof. José Luis Mascareñas.
«This is the first demonstration of a gold catalyst working inside a living cell», Dr. López says. However, there is further improvement coming from this work: in first author words, Cristian Vidal, «as soon as we confirmed that the new gold catalyst was working, the consequent goal was to combine its activity with that of a second metal catalyst, a ruthenium complex previously developed by us». Indeed, this challenge was satisfactory reached, as María Tomás highlights: «We demonstrate that both catalysts can work together simultaneously, without interfering with each other, inside the same cell».
In words of Prof. Mascareñas, «we have set the first example to create an artificial metabolism, fully compatible with natural ones and, obviously, inspired by the activity of enzymes». This work paves the way for designing new treatments based on the controlled and synchronized activation of several drugs, also having different therapeutic activities from each other.
Source: CiQUS