RT Journal Article
T1 Functional Gallic Acid-Based Dendrimers as Synthetic Nanotools to Remodel Amyloid-β-42 into Noncytotoxic Forms
A1 Rodrigues Araújo, Ana Rita
A1 Correa Chinea, Juan Francisco
A1 Domínguez Arca, Vicente
A1 Reis, Rui L.
A1 Fernández Megía, Eduardo
A1 Rodrigues Pires, Ricardo Alexandre
K1 Dendrimers
K1 Gallic acid
K1 Amyloid-β
K1 Supramolecular assembly
K1 Alzheimer’s disease
AB The self-assembly of amyloid-β (Aβ) generates cytotoxic oligomers linked to the onset and progression of Alzheimer’s disease (AD). As many fundamental molecular pathways that control Aβ aggregation are yet to be unraveled, an important strategy to control Aβ cytotoxicity is the development of bioactive synthetic nanotools capable of interacting with the heterogeneous ensemble of Aβ species and remodel them into noncytotoxic forms. Herein, the synthesis of nanosized, functional gallic acid (Ga)-based dendrimers with a precise number of Ga at their surface is described. It is shown that these Ga-terminated dendrimers interact by H-bonding with monomeric/oligomeric Aβ species at their Glu, Ala, and Asp residues, promoting their remodeling into noncytotoxic aggregates in a process controlled by the Ga units. The multivalent presentation of Ga on the dendrimer surface enhances their ability to interact with Aβ, inhibiting the primary and secondary nucleation of Aβ fibrillization and disrupting the Aβ preformed fibrils
PB ACS Publications
SN 1944-8244
YR 2021
FD 2021
LK http://hdl.handle.net/10347/28892
UL http://hdl.handle.net/10347/28892
LA eng
NO ACS Appl. Mater. Interfaces 2021, 13, 50, 59673–59682
NO The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsami.1c17823.Synthesis and characterization of dendrimers, studies of interference of dendrimers in the Aβ supramolecular assembly, and cell studies
NO The authors acknowledge the financial support from the EC (FORECAST-668983), “Programa Operacional Regional do Norte”, “Fundo Social Europeu”, Norte2020 TERM&SC, for the PhD grant NORTE-08-5369-FSE-000044, the SpanishMinistry of Science and Innovation (RTI2018-102212-B-I00), the Xunta de Galicia (ED431C 2018/30; Centro singular de investigación de Galicia accreditation 2019−2022, ED431G 2019/03), European Regional Development Fund-ERDF, and the Galician Supercomputing Centre (CESGA) and the MAT2016-80266-R of the Spanish Ministry of Science and Innovation
DS Minerva
RD 4 may 2026