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

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Tonali , N , Hericks , L , Schroeder , D C , Kracker , O , Krzemieniecki , R , Kaffy , J , Le Joncour , V , Laakkonen , P , Marion , A , Ongeri , S , Dodero , V I & Sewald , N 2021 , ' Peptidotriazolamers Inhibit A beta(1-42) Oligomerization and Cross a Blood-Brain-Barrier Model ' , ChemPlusChem , vol. 86 , no. 6 , pp. 840-851 . https://doi.org/10.1002/cplu.202000814

Titel: Peptidotriazolamers Inhibit A beta(1-42) Oligomerization and Cross a Blood-Brain-Barrier Model
Författare: Tonali, Nicolo; Hericks, Loreen; Schroeder, David C.; Kracker, Oliver; Krzemieniecki, Radoslaw; Kaffy, Julia; Le Joncour, Vadim; Laakkonen, Pirjo; Marion, Antoine; Ongeri, Sandrine; Dodero, Veronica I.; Sewald, Norbert
Upphovmannens organisation: CAN-PRO - Translational Cancer Medicine Program
Research Programs Unit
University of Helsinki
Pirjo Maarit Laakkonen / Principal Investigator
Datum: 2021-06
Språk: eng
Sidantal: 12
Tillhör serie: ChemPlusChem
ISSN: 2192-6506
DOI: https://doi.org/10.1002/cplu.202000814
Permanenta länken (URI): http://hdl.handle.net/10138/340425
Abstrakt: 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.
Subject: &#945
&#946
oligomerization inhibitors
amyloids
foldamers
peptidomimetics
peptidotriazolamers
PROTEIN-PROTEIN INTERACTIONS
BETA-HAIRPIN MIMICS
FOLDAMERS
AGGREGATION
MODULATE
3111 Biomedicine
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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