One of the main problems in pharmacology is low success rate of drug candidates in clinical trials. Despite enormous resources spent on the research and discovery of investigational drugs, especially for treatment of cancer, they still have very low success rate. The drug candidates fail mostly because of their excess toxicity.
The project addressed the problem by discovering light-controllable drug candidates, the biological activity of which can be deactivated (“switched off”) or activated (“switched on”) by non-ionisable light irradiation. The light-controllable drugs can be administered in the inactive, non-toxic form, and then activated by light only when and where required for treatment. The activation by light can be done with very high spatiotemporal precision in the lesion site, leaving the rest of the patient body unaffected. Consequently, the light-controllable drugs will have favourable pharmacological characteristics, such as high selectivity of therapeutic action, reduced overall side-toxicity and significantly augmented safety that will increase their success rate in clinical trials. As the result, the healthcare industry will obtain a new treatment modality to address unmet medical needs in Europe and in the whole world.
The main objective of the Project was the design, synthesis, as well as detailed structural and functional studies of cyclic peptide analogues (peptidomimetics), whose biological activity could be effectively controlled by light. The idea behind the design of such compounds relies on the modification of the known biologically active cyclic peptides by using photoisomerizable (photoswitchable) building blocks to get photocontrolled peptidomimetics. The modified peptides can change their structure upon irradiation with light of different wavelengths (Fig. 1), so their properties can be controlled by light. Consortium members have explored and patented the design principles which allow obtaining practically applicable photocontrolled peptidomimetics.
