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Medicinal Chemistry

The search for a good match

New drugs, like good partnerships, are built on a good match. Finding a good match between chemical substances and their targets is a typical starting point in the development of new drugs. Stefan Vogel aims to accelerate this development with a NERD grant of DKK 14 million from the Novo Nordisk Foundation.

By Birgitte Svennevig, , 1/9/2024

There is certainly a match out there. This must be reminded when searching for the right combination - also in research and development of new drugs. In the world of medicinal chemistry, many chemical substances need to be matched with a target, such as a human protein, in different ways and strengths to find a good binder in order to regulate the disease related target.

How to find the best match? This question is the starting point for Stefan Vogel's NERD project. The principle behind his idea is both simple and complex: using DNA-controlled molecular libraries to test a very large number of different chemical substances for their ability to bind to disease related protein(s).

A strong match could potentially lead to the development of a drug that can cure diseases for which there is currently no effective medical treatment. These matches are combinations that can be interesting starting structures or "drug lead candidates" as they are called in the pharmaceutical industry—chemical substances that can be further developed to drug candidates and ultimately into new medicines.

"The need for new drugs is almost endless"

"We want to make the process of finding good starting structures much faster, so medicinal research gets accelerated. The need for new and better medicine and drug candidates is almost endless," says Stefan Vogel, who is working on developing special reactors for the pursuit of these favorable combinations.

However, there are infinitely many chemical substances, so how do you test the as many combinations as possible in as little time as possible and in a sustainable manner with minimal environmental impact?

Part of Stefan Vogel's innovative solution is to conduct synthesis in ultra-small water quantities (atto- or zeptoliters). This means less compound consumption and significantly less environmental burden than traditional chemical synthesis with organic solvents.

Attoliters and zeptoliters

  • One attoliter is 0.000000000000000001 liters.

  • One zeptoliter is 0.000000000000000000001 liters.

Speed is most important

"But the most important thing is speed. We want to test thousands of chemical substances in a few minutes. Time is an extremely important factor for pharmaceutical companies because rapid development ultimately gives their product more time on the market," explains Stefan Vogel.

His nanoreactors are only 50-200 nanometers in size, so a pipette tip with water can contain many of them. Each nanoreactor is made of lipids, i.e. fat, and one should imagine a droplet with walls of fat and a content of 0.000000000000000001 liters of water plus the desired chemical substances or enzymes.

Such a nanoreactor is the same size as the structures that operate at the molecular level in an organism's cells, so one can speak of biomimetic reactors.

Merging reactors

Each nanoreactor contains chemical building blocks or enzymes that fuses if the reactor encounters another nanoreactor with a different chemical building block that it can react with when the reactors merge. This process continues until 3-5 of the original chemical building blocks have reacted with each other and become a new molecule.

The new molecules fuse also with their target (e.g. human protein) as part of the process and potential binding events can be detected for each nanoreactor individually.

"Molecules shouldn't be larger than this because then they are often no longer interesting for drug development. Some of the newly formed molecules will be able to bind to their target protein, and on an upscaled level, this chemical platform can test a very large number of different chemical substances in a very short time," says Stefan Vogel.

Scientific litterature

 Stefan Vogel has authored several scientific articles on nanoreactors, including:

Meet the researcher

Stefan Vogel is a medicinal chemist, Ph.D., and Associate Professor at the Department of Physics, Chemistry, and Pharmacy.

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About the grant

The NERD grant from the Novo Nordisk Foundation is for DKK 14 million, and the project runs until 2030. The grant supports a project aimed at developing and applying a new platform technology for DNA-controlled molecular libraries in nanoreactors. This technology holds significant potential in the search for chemical libraries of potential drug molecules that can contribute to the development of new medicines by generation of “drug lead candidates”.

Editing was completed: 09.01.2024