How repurposed molecules are set to change medicine

Spektrum der Wissenschaft

15.4.2026

Translation: machine translated

Some molecules can be turned inside out like a sock. It is not yet entirely clear what can be done with this property, but experts are already hoping for completely new approaches for medicine and technology.

There are many reasons why chemistry is so complicated. One of the most important is a phenomenon known as isomerism: molecules have the same structure but different three-dimensional shapes. And now a long-neglected version of isomerism could open up completely new avenues in medicine and technology. It involves molecules that can be turned inside out like a sock, giving them new properties. In a recent publication in the «Journal of the American Chemical Society», a team led by US chemist John A. Gladysz draws attention to the potential of such substances. According to them, this transformation could, for example, open up new design principles for macrocyclic peptides, which are currently among the most important candidates for new drugs.

The best-known example of isomers are molecules that behave like an image and its mirror image. However, molecules with the same structure can differ in many other ways. For example, DNA forms three different types of double helix, known as the A, B and Z helix. The different forms of the same substance described by Gladysz arise when an additional «handle» stretches from one side to the other over a large ring-shaped molecule. If the handle is now threaded through the ring so that it then lies on the other side of the molecule, its binding sites on the ring rotate. This changes the three-dimensional structure of the molecule and therefore presumably also how it interacts with other substances.

Gladysz and his team hope that it will be possible to construct peptides in this way that are stable enough to pass through the digestive tract and then turn into the active drug form in the body. This could solve the major problem with these active ingredients, which is that they still have to be administered directly into the bloodstream because the stomach simply digests them. As another, very practical example, the experts constructed a substance that only binds platinum and releases the metal again when it is turned inside out. This allowed platinum to be fished out of a mixture of different metals and enriched separately.

Unlike other molecules that selectively bind metals, this concept does not require a separate step to separate the two. However, some very fundamental questions remain unanswered. For example, it is still unclear how the shape change can be measured and controlled, and which of the two shapes has which effect on existing inverted molecules. Last but not least, experts still need to think about how the various emerging molecular versions - and future, even more complex inverted pomers - can be named in a standardised and unambiguous way.

Spectrum of Science

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