Infrared sensor serves as a new tool for drug discovery

August 28, 2018, CORDIS
Infrared sensor serves as a new tool for drug discovery
Credit: Sisacom, Shutterstock

Scientists have found a new method for analysing how active agents affect a specific protein essential for cell survival. Their research could help to quickly develop drugs with fewer side effects.

The efficacy of many drugs is based on how they manipulate the metabolism of cells by inhibiting the activity of specific proteins. However, analyses of an active agent's impact on the structure of its target protein have generally used time-consuming and material-intensive procedures.

A team of researchers supported by the EU-funded K4DD project has introduced an alternative way of examining such interactions using an . The study was published recently in the journal Angewandte Chemie.

The new method provides information on structural changes in target proteins within minutes and can help narrow down the type of structural change, as stated in a press release by the Ruhr Universität Bochum (RUB). "The sensor is based on a crystal that is permeable for infrared light. The protein is bound on its surface. Infrared spectra are recorded through the crystal, while the surface is rinsed with solutions with or without any ."

Heat shock protein

In the journal article the researchers said the investigation of "protein–ligand interactions is crucial during early drug discovery processes." To demonstrate the reliability of their method, they immobilised the HSP90 on an attenuated total reflectance crystal. "This protein is an important molecular target for drugs against several diseases including cancer. With our novel approach we investigated a ligand-induced secondary structural change." The team analysed two specific binding modes of 19 drug-like compounds. "Different binding modes can lead to different efficacy and specificity of different drugs."

The RUB press release refers to HSP90 as a "folding helper that assists newly generated proteins in the cell to form the correct three-dimensional structure." It adds: "Due to their extremely active metabolism, tumour cells require it very urgently. HSP90-inhibiting active agents constitute an approach for the development of drugs that stop tumour growth."

The press release also notes that the sensor detects changes in the protein's spectral area that is structure-sensitive, the so-called amid region. This is characteristic of a protein's scaffold. "If any changes occur, it is obvious that the active agent has altered the shape of the protein." Project supervisor Prof. Dr. Klaus Gerwert, explains: "Since our sensor acts as a flow system, we can rinse the active agents off the target protein after binding and, consequently, measure how the efficacy changes over time."

One parameter affecting drug efficacy is the life span of the complex formed between a drug and its , whose function must be altered. Active agents that are bound to this protein for a long time could remain effective for an extended period. Tablets with such active agents have to be taken only once a day and they often have fewer side effects, the researchers say. In the journal article they conclude: "Particularly when scaled up in an automated screening platform, our method could be used to identify new drug candidates in the early drug-discovery process."

The research into the infrared sensor was performed under K4DD (Kinetics for Drug Discovery (K4DD)). The project sought to improve the understanding of how potential drugs bind with their target. It was also aimed at developing tools to help researchers determine whether a drug candidate is likely to be safe and effective much earlier in its development process.

Explore further: Infrared sensor as new method for drug discovery

More information: K4DD project website: www.k4dd.eu/home/ Jörn Güldenhaupt et al.

Ligand-Induced Conformational Changes in HSP90 Monitored Time Resolved and Label Free-Towards a Conformational Activity Screening for Drug Discovery, Angewandte Chemie International Edition (2018). DOI: 10.1002/anie.201802603

Related Stories

Infrared sensor as new method for drug discovery

July 19, 2018

Using an infrared sensor, biophysicists at Ruhr-Universität Bochum (RUB) have succeeded in analysing quickly and easily which active agents affect the structure of proteins and how long that effect lasts. Thus, Prof Dr. ...

New computational method for drug discovery

July 12, 2018

HITS researchers developed tauRAMD, a tool to predict drug-target residence times from short simulations. The method is illustrated on the cover page of July 2018 issue of the Journal of Chemical Theory and Computation, software ...

Recommended for you

Meteorite source in asteroid belt not a single debris field

February 17, 2019

A new study published online in Meteoritics and Planetary Science finds that our most common meteorites, those known as L chondrites, come from at least two different debris fields in the asteroid belt. The belt contains ...

Diagnosing 'art acne' in Georgia O'Keeffe's paintings

February 17, 2019

Even Georgia O'Keeffe noticed the pin-sized blisters bubbling on the surface of her paintings. For decades, conservationists and scholars assumed these tiny protrusions were grains of sand, kicked up from the New Mexico desert ...

Archaeologists discover Incan tomb in Peru

February 16, 2019

Peruvian archaeologists discovered an Incan tomb in the north of the country where an elite member of the pre-Columbian empire was buried, one of the investigators announced Friday.

Where is the universe hiding its missing mass?

February 15, 2019

Astronomers have spent decades looking for something that sounds like it would be hard to miss: about a third of the "normal" matter in the Universe. New results from NASA's Chandra X-ray Observatory may have helped them ...

What rising seas mean for local economies

February 15, 2019

Impacts from climate change are not always easy to see. But for many local businesses in coastal communities across the United States, the evidence is right outside their doors—or in their parking lots.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.