{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:06:20Z","timestamp":1773277580811,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-64-46027"],"award-info":[{"award-number":["20-64-46027"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sources of evidence suggest that soluble amyloid \u03b2 (A\u03b2)-oligomers are responsible for the development and progression of Alzheimer\u2019s disease (AD). In order to specifically eliminate these toxic A\u03b2-oligomers, our group has developed a variety of all-d-peptides over the past years. One of them, RD2, has been intensively studied and showed such convincing in vitro and in vivo properties that it is currently in clinical trials. In order to further optimize the compounds and to elucidate the characteristics of therapeutic d-peptides, several rational drug design approaches have been performed. Two of these d-peptides are the linear tandem (head-to-tail) d-peptide RD2D3 and its cyclized form cRD2D3. Tandemization and cyclization should result in an increased in vitro potency and increase pharmacokinetic properties, especially crossing the blood\u2013brain-barrier. In comparison, cRD2D3 showed a superior pharmacokinetic profile to RD2D3. This fact suggests that higher efficacy can be achieved in vivo at equally administered concentrations. To prove this hypothesis, we first established the in vitro profile of both d-peptides here. Subsequently, we performed an intraperitoneal treatment study. This study failed to provide evidence that cRD2D3 is superior to RD2D3 in vivo as in some tests cRD2D3 failed to show equal or higher efficacy.<\/jats:p>","DOI":"10.3390\/ijms22126553","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T11:19:20Z","timestamp":1624015160000},"page":"6553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["In Vitro and In Vivo Efficacies of the Linear and the Cyclic Version of an All-d-Enantiomeric Peptide Developed for the Treatment of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Sarah","family":"Schemmert","sequence":"first","affiliation":[{"name":"Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luana Cristina","family":"Camargo","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"},{"name":"Institut f\u00fcr Physikalische Biologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Honold","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0965-3908","authenticated-orcid":false,"given":"Ian","family":"Gering","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0271-7390","authenticated-orcid":false,"given":"Janine","family":"Kutzsche","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-0755","authenticated-orcid":false,"given":"Antje","family":"Willuweit","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Medical Imaging Physics (INM-4), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0065-7366","authenticated-orcid":false,"given":"Dieter","family":"Willbold","sequence":"additional","affiliation":[{"name":"Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum J\u00fclich, 52425 J\u00fclich, Germany"},{"name":"Institut f\u00fcr Physikalische Biologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101045","DOI":"10.1016\/j.arr.2020.101045","article-title":"Prevention of dementia in an ageing world: Evidence and biological rationale","volume":"64","author":"Grande","year":"2020","journal-title":"Ageing Res. 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