Peptidotriazolamers Inhibit A beta(1-42) Oligomerization and Cross a Blood-Brain-Barrier Model

2021-05-01
Tonali, Nicolo
Hericks, Loreen
Schroeder, David C.
Kracker, Oliver
Krzemieniecki, Radoslaw
Kaffy, Julia
Le Joncour, Vadim
Laakkonen, Pirjo
Marıon, Antoıne
Ongeri, Sandrine
Dodero, Veronica I.
Sewald, Norbert
In peptidotriazolamers every second peptide bond is replaced by a 1H-1,2,3-triazole. Such foldamers are expected to bridge the gap in molecular weight between small-molecule drugs and protein-based drugs. Amyloid beta (A beta) aggregates play an important role in Alzheimer's disease. We studied the impact of amide bond replacements by 1,4-disubstituted 1H-1,2,3-triazoles on the inhibitory activity of the aggregation "hot spots" (KLVFF20)-L-16 and G(39)VVIA(42) in A beta(1-42). We found that peptidotriazolamers act as modulators of the A beta(1-42) oligomerization. Some peptidotriazolamers are able to interfere with the formation of toxic early A beta 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.
CHEMPLUSCHEM

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Citation Formats
N. Tonali et al., “Peptidotriazolamers Inhibit A beta(1-42) Oligomerization and Cross a Blood-Brain-Barrier Model,” CHEMPLUSCHEM, pp. 0–0, 2021, Accessed: 00, 2021. [Online]. Available: https://hdl.handle.net/11511/90521.