title: Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent Photodynamic Cancer Therapy.
abstract: Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene-derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light-sensitive molecule is not a mediator but is itself the cytotoxic agent. As a derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic exists in two thermally stable photoforms that are interconvertible by light of different wavelengths. The isomer generated by visible light shows much stronger toxicity against tumor cells than the UV-generated isomer. First in vivo applications are demonstrated on a tumor animal model to illustrate how the peptidomimetic can be administered in the less toxic form and then activated locally in a solid tumor by visible light.
authors.affiliation: Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany.
authors.forename: Oleg
authors.initials: O
authors.lastname: Babii
authors.affiliation: Institute of Biological Interfaces (IBG-2), KIT, POB 3640, 76021, Karlsruhe, Germany.
authors.forename: Sergii
authors.initials: S
authors.lastname: Afonin
authors.affiliation: Institute of Biology, TSNUK, prosp. Hlushkova 2, 03022, Kyiv, Ukraine.
authors.forename: Liudmyla V
authors.initials: LV
authors.lastname: Garmanchuk
authors.affiliation: Institute of Biology, TSNUK, prosp. Hlushkova 2, 03022, Kyiv, Ukraine.
authors.forename: Viktoria V
authors.initials: VV
authors.lastname: Nikulina
authors.affiliation: Institute of Biology, TSNUK, prosp. Hlushkova 2, 03022, Kyiv, Ukraine.
authors.forename: Tetiana V
authors.initials: TV
authors.lastname: Nikolaienko
authors.affiliation: Institute of Biology, TSNUK, prosp. Hlushkova 2, 03022, Kyiv, Ukraine.
authors.forename: Olha V
authors.initials: OV
authors.lastname: Storozhuk
authors.affiliation: Institute of Biology, TSNUK, prosp. Hlushkova 2, 03022, Kyiv, Ukraine.
authors.forename: Dmytro V
authors.initials: DV
authors.lastname: Shelest
authors.affiliation: Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine (NASU), vul. Vasylkivska 45, 03022, Kyiv, Ukraine.
authors.forename: Olga I
authors.initials: OI
authors.lastname: Dasyukevich
authors.affiliation: Institute of Biology, TSNUK, prosp. Hlushkova 2, 03022, Kyiv, Ukraine.
authors.forename: Liudmyla I
authors.initials: LI
authors.lastname: Ostapchenko
authors.affiliation: Enamine Ltd., vul. Matrosova 23, 01103, Kyiv, Ukraine.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Iurchenko
authors.affiliation: Enamine Ltd., vul. Matrosova 23, 01103, Kyiv, Ukraine.
authors.forename: Sergey
authors.initials: S
authors.lastname: Zozulya
authors.affiliation: Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131, Karlsruhe, Germany. Anne.Ulrich@kit.edu.|Institute of Biological Interfaces (IBG-2), KIT, POB 3640, 76021, Karlsruhe, Germany. Anne.Ulrich@kit.edu.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.affiliation: Institute of High Technologies (IHT), Taras Shevchenko National University of Kyiv (TSNUK), vul. Volodymyrska 60, 01601, Kyiv, Ukraine. ik214@yahoo.com.
authors.forename: Igor V
authors.identifier: 0000-0002-7908-9145
authors.initials: IV
authors.lastname: Komarov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D010100:Oxygen / Q000737:chemistry*; D057786:Peptidomimetics; D055668:Photochemical Processes; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D057786:Peptidomimetics; D017319:Photosensitizing Agents; D010100:Oxygen
keywords: cancer; drug design; peptidomimetics; photodynamic therapy; photoswitches