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@ARTICLE{Kagan:8402,
      author       = {Kagan, V.E. and Wipf, P. and Stoyanovsky, D. and
                      Greenberger, J.S. and Borisenko, G. and Belikova, N.A. and
                      Yanamala, N. and Samhan Arias, A.K. and Tungekar, M.A. and
                      Jiang, J. and Tyurina, Y.Y. and Ji, J. and
                      Klein-Seetharaman, J. and Pitt, B.R. and Shvedova, A.A. and
                      Bayir, H.},
      title        = {{M}itochondrial targeting of electron scavenging
                      antioxidants: {R}egulation of selective oxidation vs random
                      chain reactions},
      journal      = {Advanced drug delivery reviews},
      volume       = {61},
      issn         = {0169-409X},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {PreJuSER-8402},
      pages        = {1375 - 1385},
      year         = {2009},
      note         = {This work was supported by NIH Grants U19 AIO68021,
                      HL70755, HD057587, NS061817, NORA 927Z1LU, PittGrid
                      (http://www.pittgrid. pitt.edu) and la junta de Extremadura
                      -Consejeria de Infraestructuras y Desarrollo Tecnologico- y
                      el Fondo Social Europeo (Orden 2008050288).},
      abstract     = {Effective regulation of highly compartmentalized production
                      of reactive oxygen species and peroxidation reactions in
                      mitochondria requires targeting of small molecule
                      antioxidants and antioxidant enzymes into the organelles.
                      This review describes recently developed approaches to
                      mitochondrial targeting of small biologically active
                      molecules based on: (i) preferential accumulation in
                      mitochondria because of their hydrophobicity and positive
                      charge (hydrophobic cations), (ii) binding with high
                      affinity to an intra-mitochondrial constituent, and (iii)
                      metabolic conversions by specific mitochondrial enzymes to
                      reveal an active entity. In addition, targeted delivery of
                      antioxidant enzymes via expression of leader sequences
                      directing the proteins into mitochondria is considered.
                      Examples of successful antioxidant and anti-apoptotic
                      protection based on the ability of targeted cargoes to
                      inhibit cytochrome c-catalyzed peroxidation of a
                      mitochondria-specific phospholipid cardiolipin, in vitro and
                      in vivo are presented. Particular emphasis is placed on the
                      employment of triphenylphosphonium- and hemi-gramicidin
                      S-moieties as two effective vehicles for mitochondrial
                      delivery of antioxidants.},
      keywords     = {Animals / Antioxidants: pharmacology / Apoptosis: drug
                      effects / Drug Delivery Systems: methods / Electron
                      Transport Complex I: metabolism / Free Radical Scavengers:
                      chemistry / Free Radical Scavengers: pharmacokinetics /
                      Humans / Mitochondria: drug effects / Mitochondria:
                      metabolism / Models, Biological / Molecular Structure /
                      Oxidation-Reduction: drug effects / Oxidative Stress: drug
                      effects / Reactive Oxygen Species: metabolism / Antioxidants
                      (NLM Chemicals) / Free Radical Scavengers (NLM Chemicals) /
                      Reactive Oxygen Species (NLM Chemicals) / Electron Transport
                      Complex I (NLM Chemicals) / J (WoSType)},
      cin          = {ISB-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ISB-2-20090406},
      pnm          = {Programm Biosoft},
      pid          = {G:(DE-Juel1)FUEK443},
      shelfmark    = {Pharmacology $\&$ Pharmacy},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:19716396},
      pmc          = {pmc:PMC2784017},
      UT           = {WOS:000272600300014},
      doi          = {10.1016/j.addr.2009.06.008},
      url          = {https://juser.fz-juelich.de/record/8402},
}