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Eur J Med Chem. 2014 Oct 6;85:43-50. doi: 10.1016/j.ejmech.2014.07.085. Epub 2014 Jul 24.

Nanoliposomes presenting on surface a cis-glycofused benzopyran compound display binding affinity and aggregation inhibition ability towards Amyloid β1-42 peptide.

Author information

1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
2
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Patras, Greece.
3
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy; Department of Chemistry, University of Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro, Portugal.
4
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Patras, Greece; Institute of Chemical Engineering and Sciences, FORTH/ICES, Rio 26504, Patras, Greece.
5
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy. Electronic address: barbara.laferla@unimib.it.

Abstract

Nanoliposomes decorated on their surface with ligands for Aβ-peptides, the key morphological features of Alzheimer's disease (AD), have been synthesized and characterized for their ability to target Aβ-peptide aggregates. A tricyclic benzopyrane-glycofused structure has been exploited as Aβ-peptide ligand, which was linked to liposomes via a copper-free, chemoselective, biocompatible click chemistry reaction. The tricyclic-decorated liposomes presented a mean diameter in the nanomolar range (150-200 nm), a negative z-potential and a good stability, at least up to one month. Integrity studies performed in the presence of serum proteins indicated that these decorated nanoliposomes fulfill the requirements for in vivo applications. NMR experiments carried out with Aβ1-42 oligomers using both surface functionalized and plain (control) liposomes, revealed that the binding ability of the nanoliposomes was mediated by the presence of the tricyclic ligand on their surface. Finally ThT assay carried out with tricyclic-decorated liposomes showed significant decrease in thioflavine T fluorescence after 24 h, suggesting a significant inhibition/delay of Aβ1-42 aggregation.

KEYWORDS:

Alzheimer disease (AD); Amyloid β (Aβ); Copper-free click chemistry; Glycoderivatives; Liposomes; NMR interaction studies

PMID:
25072875
DOI:
10.1016/j.ejmech.2014.07.085
[Indexed for MEDLINE]

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