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@ARTICLE{Elfgen:836466,
      author       = {Elfgen, Anne and Santiago-Schübel, Beatrix and Gremer,
                      Lothar and Kutzsche, Janine and Willbold, Dieter},
      title        = {{S}urprisingly high stability of the {A}β oligomer
                      eliminating all-d-enantiomeric peptide {D}3 in media
                      simulating the route of orally administered drugs},
      journal      = {European journal of pharmaceutical sciences},
      volume       = {107},
      issn         = {0928-0987},
      address      = {New York, NY [u.a.]},
      publisher    = {Elsevier},
      reportid     = {FZJ-2017-05584},
      pages        = {203-207},
      year         = {2017},
      abstract     = {The aggregation of the amyloid β protein (Aβ) plays an
                      important role in the pathology of Alzheimer's disease.
                      Previously, we have developed the all-d-enantiomeric peptide
                      D3, which is able to eliminate neurotoxic Aβ oligomers in
                      vitro and improve cognition in a transgenic Alzheimer's
                      disease mouse model in vivo even after oral administration.
                      d-Peptides are expected to be more resistant against
                      enzymatic proteolysis compared to their l-enantiomeric
                      equivalents, and indeed, a pharmacokinetic study with
                      tritiated D3 revealed the oral bioavailability to be about
                      $58\%.$ To further investigate the underlying properties, we
                      examined the stability of D3 in comparison to its
                      corresponding all-l-enantiomeric mirror image l-D3 in media
                      simulating the gastrointestinal tract, blood and liver.
                      Potential metabolization was followed by reversed-phase
                      high-performance liquid chromatography. In simulated gastric
                      fluid, D3 remained almost completely stable $(89\%)$ within
                      24 h, while $70\%$ of l-D3 was degraded within the same time
                      period. Notably, in simulated intestinal fluid, D3 also
                      remained stable $(96\%)$ for 24 h, whereas l-D3 was
                      completely metabolized within seconds. In human plasma and
                      human liver microsomes, l-D3 was metabolized several hundred
                      times faster than D3. The remarkably high stability may
                      explain the high oral bioavailability seen in previous
                      studies allowing oral administration of the drug candidate.
                      Thus, all-d-enantiomeric peptides may represent a promising
                      new compound class for drug development.},
      cin          = {ICS-6 / ZEA-3},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)ZEA-3-20090406},
      pnm          = {553 - Physical Basis of Diseases (POF3-553)},
      pid          = {G:(DE-HGF)POF3-553},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000407836700020},
      pubmed       = {pmid:28711713},
      doi          = {10.1016/j.ejps.2017.07.015},
      url          = {https://juser.fz-juelich.de/record/836466},
}