title: Switchable photooxygenation catalysts that sense higher-order amyloid structures.
abstract: Proteins can misfold into amyloid structures that are associated with diseases; however, the same proteins often have important biological roles. To degrade selectively the amyloid form without affecting the fraction of functional protein is, therefore, an attractive goal. Here we report target-state-dependent photooxygenation catalysts that are active only when bound to the cross-β-sheet structure that is characteristic of pathogenic aggregated amyloid proteins. We show these catalysts can selectively oxygenate the amyloid form of amyloid β-protein (Aβ) 1-42 in the presence of non-amyloid off-target substrates. Furthermore, photooxygenation with a catalyst that bears an Aβ-binding peptide attenuated the Aβ pathogenicity in the presence of cells. We also show that selective photooxygenation is generally applicable to other amyloidogenic proteins (amylin, insulin, β2-microglobulin, transthyretin and α-synuclein) and does not affect the physiologically functional non-aggregate states of these proteins. This is the first report of an artificial catalyst that can be selectively and reversibly turned on and off depending on the structure and aggregation state of the substrate protein.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|ERATO, Japan Science and Technology Agency (JST), Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Taniguchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Oisaki
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|ERATO, Japan Science and Technology Agency (JST), Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Sohma
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|ERATO, Japan Science and Technology Agency (JST), Kanai Life Science Catalysis Project, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Kanai
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects / Q000633:toxicity; D002384:Catalysis; D015195:Drug Design; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism; D008027:Light; D008956:Models, Chemical; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects / Q000633:toxicity; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D011789:Quantum Theory; D051381:Rats; D026082:Singlet Oxygen / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009842:Oligopeptides; D010446:Peptide Fragments; D011228:Prealbumin; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D001613:beta 2-Microglobulin; D026082:Singlet Oxygen