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| 100 | 1 | _ | |a Schartmann, Elena |0 P:(DE-Juel1)166069 |b 0 |
| 245 | _ | _ | |a Comparison of blood-brain barrier penetration efficiencies between linear and cyclic all- d -enantiomeric peptides developed for the treatment of Alzheimer's disease |
| 260 | _ | _ | |a New York, NY [u.a.] |c 2018 |b Elsevier |
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| 520 | _ | _ | |a Alzheimer's disease (AD), until now, is an incurable progressive neurodegenerative disease. To target toxic amyloid β oligomers in AD patients' brains and to convert them into non-toxic aggregation-incompetent species, we designed peptides consisting solely of d-enantiomeric amino acid residues. The original lead compound was named D3 and several D3 derivatives were designed to enhance beneficial properties. Here, we compare four d-peptides concerning their efficiencies to pass the blood-brain barrier (BBB). We demonstrate that the d-peptides' concentrations in murine brain directly correlate with concentrations in cerebrospinal fluid. The cyclic d-enantiomeric peptide cRD2D3 is characterized by the highest efficiency to pass the BBB. For in total three cyclic peptides we show that administration of cyclic peptides resulted in up to tenfold higher peak concentrations in brain as compared to their linear equivalents which have partially been characterized before (Jiang et al., 2015; Leithold et al., 2016a). These results suggest that cyclic peptides pass the murine BBB more efficiently than their linear equivalents. cRD2D3's proteolytic stability, oral bioavailability, long duration of action and its favorable brain/plasma ratio reveal that it may become a suitable drug for long-term AD-treatment from a pharmacokinetic point of view. |
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| 700 | 1 | _ | |a Schemmert, Sarah |0 P:(DE-Juel1)165908 |b 1 |
| 700 | 1 | _ | |a Ziehm, Tamar |0 P:(DE-Juel1)162487 |b 2 |
| 700 | 1 | _ | |a Leithold, Leonie H. E. |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Jiang, Nan |0 P:(DE-Juel1)145884 |b 4 |
| 700 | 1 | _ | |a Tusche, Markus |0 P:(DE-Juel1)131709 |b 5 |
| 700 | 1 | _ | |a Shah, N. J. |0 P:(DE-Juel1)131794 |b 6 |
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| 700 | 1 | _ | |a Willbold, Dieter |0 P:(DE-Juel1)132029 |b 9 |e Corresponding author |u fzj |
| 700 | 1 | _ | |a Willuweit, Antje |0 P:(DE-Juel1)144347 |b 10 |e Corresponding author |
| 773 | _ | _ | |a 10.1016/j.ejps.2017.12.005 |g Vol. 114, p. 93 - 102 |0 PERI:(DE-600)1483522-8 |p 93 - 102 |t European journal of pharmaceutical sciences |v 114 |y 2018 |x 0928-0987 |
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