دورية أكاديمية
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Metabolic resistance of the D-peptide RD2 developed for direct elimination of amyloid-β oligomers.

التفاصيل البيبلوغرافية
العنوان: Metabolic resistance of the D-peptide RD2 developed for direct elimination of amyloid-β oligomers.
المؤلفون: Elfgen A; Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Center Jülich, 52428, Jülich, Germany., Hupert M; Central Institute for Engineering, Electronics and Analytics (ZEA-3), Research Center Jülich, 52428, Jülich, Germany., Bochinsky K; Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Center Jülich, 52428, Jülich, Germany., Tusche M; Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Center Jülich, 52428, Jülich, Germany., González de San Román Martin E; Central Institute for Engineering, Electronics and Analytics (ZEA-3), Research Center Jülich, 52428, Jülich, Germany., Gering I; Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Center Jülich, 52428, Jülich, Germany., Sacchi S; Dipartimento di Biotecnologie e Scienze della Vita, Università dell'Insubria, 21100, Varese, Italy.; The Protein Factory Research Center, Università dell'Insubria and Politecnico di Milano, 20100, Milano, Italy., Pollegioni L; Dipartimento di Biotecnologie e Scienze della Vita, Università dell'Insubria, 21100, Varese, Italy.; The Protein Factory Research Center, Università dell'Insubria and Politecnico di Milano, 20100, Milano, Italy., Huesgen PF; Central Institute for Engineering, Electronics and Analytics (ZEA-3), Research Center Jülich, 52428, Jülich, Germany., Hartmann R; Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Center Jülich, 52428, Jülich, Germany., Santiago-Schübel B; Central Institute for Engineering, Electronics and Analytics (ZEA-3), Research Center Jülich, 52428, Jülich, Germany., Kutzsche J; Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Center Jülich, 52428, Jülich, Germany. j.kutzsche@fz-juelich.de.; Central Institute for Engineering, Electronics and Analytics (ZEA-3), Research Center Jülich, 52428, Jülich, Germany. j.kutzsche@fz-juelich.de., Willbold D; Institute of Complex Systems, Structural Biochemistry (ICS-6), Research Center Jülich, 52428, Jülich, Germany. d.willbold@fz-juelich.de.; Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany. d.willbold@fz-juelich.de.
المصدر: Scientific reports [Sci Rep] 2019 Apr 05; Vol. 9 (1), pp. 5715. Date of Electronic Publication: 2019 Apr 05.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Amyloid beta-Peptides/*metabolism , Gastrointestinal Tract/*drug effects , Liver/*drug effects , Oligopeptides/*pharmacokinetics, Animals ; Culture Media ; Gastrointestinal Tract/metabolism ; Humans ; Liver/metabolism ; Rats
مستخلص: Alzheimer's disease (AD) is a neurodegenerative disorder leading to dementia. Aggregation of the amyloid-β peptide (Aβ) plays an important role in the disease, with Aβ oligomers representing the most toxic species. Previously, we have developed the Aβ oligomer eliminating therapeutic compound RD2 consisting solely of D-enantiomeric amino acid residues. RD2 has been described to have an oral bioavailability of more than 75% and to improve cognition in transgenic Alzheimer's disease mouse models after oral administration. In the present study, we further examined the stability of RD2 in simulated gastrointestinal fluids, blood plasma and liver microsomes. In addition, we have examined whether RD2 is a substrate for the human D-amino acid oxidase (hDAAO). Furthermore, metabolite profiles of RD2 incubated in human, rodent and non-rodent liver microsomes were compared across species to search for human-specific metabolites that might possibly constitute a threat when applying the compound in humans. RD2 was remarkably resistant against metabolization in all investigated media and not converted by hDAAO. Moreover, RD2 did not influence the activity of any of the tested enzymes. In conclusion, the high stability and the absence of relevant human-specific metabolites support RD2 to be safe for oral administration in humans.
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المشرفين على المادة: 0 (Amyloid beta-Peptides)
0 (Culture Media)
0 (Oligopeptides)
0 (RD2 peptide)
تواريخ الأحداث: Date Created: 20190407 Date Completed: 20201014 Latest Revision: 20210109
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6450887
DOI: 10.1038/s41598-019-41993-6
PMID: 30952881
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-019-41993-6