12516548_1179137922097935_388707243_nA group of researchers at the University of Kiev and scientists of the KIT(Karlsruhe Institute of Technology)have made an antibiotic, whose biological activity can be managed by light.Thanks to the robust diarylethenephotoswitch, the antimicrobial effect of the peptide mimetic can be applied in a spatially and temporally specific manner.  This discovery can open up new ways for the treatment of local infections while reducing side effects at the same time. The researchers unveiled the photoactivable antibiotic along with the new photomodule in the “Very important paper” of the journal AngewandteChemie.

If these photoswitch-able molecules are exposed to light of an adequate wavelength they can change their structure and properties. Among the photoswitches known are diarylethenes.

By reversible photo isomerization, i.e. a reversible light-induced internal relocation of the molecule, the open form is turned into a closed form. Such photo switchable molecules are applied in molecular electronics and many other areas. Particularly interesting opportunities result from the insertion of photo switches into biomolecules to control their activity by light. Interest focuses on so-called peptide mimetics, compounds whose major structural elements emulate a peptide (small protein).

Proffesor Anne S. Ulrich, Director of the Institute for Biological Interfaces 2 (IBG2) and holder of the Chair for Biochemistry at the Institute of Organic Chemistry (IOC) of KIT, and her colleagues have made, for the first time, a photo switchable peptide mimetic based on a diarylethene scaffold that can be photo isomerized reversibly.  This building block was modified into an amino acid analog and it was incorporated directly into the backbone of the annular peptide antibiotic Gramicidin S. The biological activity of the resulting peptide mimetic can be controlled spatially and temporally with the help of visible and UV light. The research group treated a bacterial film with the inactivated antibiotic and exposed it to light via a mask. As a result, the structure of the photo switchable diarylethene changed from closed to an open form.

This structural modification resulted in a much higher antimicrobial effect.  “In the future, such photoactivable antibiotics might be used as smart therapeutic agents against local bacterial infections,” Professor Anne S. Ulrich explains. “Usual side effects can also be minimized by switching.” Based on this strategy, new peptide-based agents against cancer might be feasible, as the newly developed photoactivable building block can also be applied in other peptide sequences.

 

References:

·         “Controlling Biological Activity with Light: Diarylethene-Containing Cyclic Peptidomimetics” by Oleg Babii, SergiiAfonin, Marina Berditsch, Sabine Reißer, Pavel K. Mykhailiuk, Vladimir S. Kubyshkin, Thomas Steinbrecher, Anne S. Ulrich, and Igor V. Komarov in AngewandteChemie

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·         http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-3757