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@ARTICLE{Schemmert:894084,
author = {Schemmert, Sarah and Camargo, Luana Cristina and Honold,
Dominik and Gering, Ian and Kutzsche, Janine and Willuweit,
Antje and Willbold, Dieter},
title = {{I}n {V}itro and {I}n {V}ivo {E}fficacies of the {L}inear
and the {C}yclic {V}ersion of an {A}ll-d-{E}nantiomeric
{P}eptide {D}eveloped for the {T}reatment of {A}lzheimer’s
{D}isease},
journal = {International journal of molecular sciences},
volume = {22},
number = {12},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {FZJ-2021-03030},
pages = {6553 -},
year = {2021},
abstract = {Multiple sources of evidence suggest that soluble amyloid
β (Aβ)-oligomers are responsible for the development and
progression of Alzheimer’s disease (AD). In order to
specifically eliminate these toxic Aβ-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–brain-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.},
cin = {IBI-7 / INM-4},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312 / I:(DE-Juel1)INM-4-20090406},
pnm = {323 - Molecular Targets $\&$ Therapies (POF4-323) / 5244 -
Information Processing in Neuronal Networks (POF4-524)},
pid = {G:(DE-HGF)POF4-323 / G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {34207233},
UT = {WOS:000665922100001},
doi = {10.3390/ijms22126553},
url = {https://juser.fz-juelich.de/record/894084},
}