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Peptidotriazolamers Inhibit Aβ(1–42) Oligomerization and Cross a Blood‐Brain‐Barrier Model
Author(s) -
Tonali Nicolo,
Hericks Loreen,
Schröder David C.,
Kracker Oliver,
Krzemieniecki Radosław,
Kaffy Julia,
Le Joncour Vadim,
Laakkonen Pirjo,
Marion Antoine,
Ongeri Sandrine,
Dodero Veronica I.,
Sewald Norbert
Publication year - 2021
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.202000814
Subject(s) - chemistry , in vitro , blood–brain barrier , peptide , amide , small molecule , stereochemistry , peptide bond , molecule , combinatorial chemistry , biophysics , biochemistry , neuroscience , central nervous system , organic chemistry , biology
In peptidotriazolamers every second peptide bond is replaced by a 1 H ‐1,2,3‐triazole. Such foldamers are expected to bridge the gap in molecular weight between small‐molecule drugs and protein‐based drugs. Amyloid β (Aβ) aggregates play an important role in Alzheimer's disease. We studied the impact of amide bond replacements by 1,4‐disubstituted 1 H ‐1,2,3‐triazoles on the inhibitory activity of the aggregation “hot spots” K 16 LVFF 20 and G 39 VVIA 42 in Aβ(1–42). We found that peptidotriazolamers act as modulators of the Aβ(1–42) oligomerization. Some peptidotriazolamers are able to interfere with the formation of toxic early Aβ oligomers, depending on the position of the triazoles, which is also supported by computational studies. Preliminary in vitro results demonstrate that a highly active peptidotriazolamer is also able to cross the blood‐brain‐barrier.