Switching drugs on and off with light

Swiss researchers have filmed for the first time how a drug was activated in the body with light. This film could give the development of such drugs a decisive boost.

Scientists Jörg Standfuss and Maximilian Wranik

With so-called photopharmacological drugs, the active ingredient is activated with a light pulse only when it has reached the place in the body where it is supposed to act - and when its task is done, it can also be switched off again with another light pulse, said a statement from the Paul Scherrer Institute (PSI). This new type of drug could limit possible side effects and reduce the development of resistance.

The PSI researchers have made this process visible for the first time in the world using the Swiss X-ray free-electron laser SwissFEL and the Swiss Synchrotron Light Source SLS. In future, active substances can be made more suitable in this way. "If we know how the molecule behaves, we can adjust the chemistry," explained Jörg Standfuss, co-author of the study.

Light switch on cancer drug

To make drugs light-sensitive, a switch molecule that reacts to light is built into conventional drugs. For their study, the researchers used the drug Combretastatin A-4, which - without a light switch - is currently being tested in clinical trials as an anti-cancer drug.

The switch molecule holds the active substance stretched into an elongated chain. In response to the light impulse, the compound bends and brings both ends of the chain closer together - like a muscle that reflexively contracts and thereby flexes a joint. This is the only way the active ingredient fits into the so-called binding pocket, which are depressions on the protein surface to which the molecule docks in order to unfold its effect.

Written by: sda

Photos: PSI/Markus Fischer

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