Peptidotriazolamers Inhibit Aβ(1-42) Oligomerization and Cross a Blood-Brain-Barrier Model.


Tonali N., Hericks L., Schroeder D. C., Kracker O., Krzemieniecki R., Kaffy J., ...Daha Fazla

ChemPlusChem, cilt.86, ss.840-851, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 86
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/cplu.202000814
  • Dergi Adı: ChemPlusChem
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.840-851
  • Anahtar Kelimeler: &#945, &#946, oligomerization inhibitors, amyloids, foldamers, peptidomimetics, peptidotriazolamers, PROTEIN-PROTEIN INTERACTIONS, BETA-HAIRPIN MIMICS, FOLDAMERS, AGGREGATION, MODULATE
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

© 2021 The Authors. ChemPlusChem published by Wiley-VCH GmbHIn 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 β (Aβ) 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” K16LVFF20 and G39VVIA42 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.