TY  - JOUR
AU  - Bartus, Éva
AU  - Olajos, Gábor
AU  - Schuster, Ildikó
AU  - Bozsó, Zsolt
AU  - Deli, Mária Anna
AU  - Veszelka, Szilvia
AU  - Walter, Fruzsina
AU  - Datki, Zsolt László
AU  - Szakonyi, Zsolt
AU  - Martinek, Tamás
AU  - Fülöp, Lívia
TI  - Structural optimization of foldamer-dendrimer conjugates as multivalent agents against the toxic effects of amyloid beta oligomers
JF  - MOLECULES
J2  - MOLECULES
VL  - 23
ET  - 0
PY  - 2018
IS  - 10
PG  - 14
SN  - 1420-3049
DO  - 10.3390/molecules23102523
UR  - https://m2.mtmt.hu/api/publication/30310687
ID  - 30310687
N1  - Funding Agency and Grant Number: National Research, Development and Innovation Office [GINOP-2.2.1-15-2016-00007]; Hungarian Brain Research Program I and II [KTIA_13_NAP-A-III/7, 2017-1.2.1-NKP-2017-00002]; Talentum Foundation of Gedeon Richter Ltd.; Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences [BO/00724/12]; Hungarian Scientific Research Fund [OTKA PD105622]
AB  - Alzheimer's disease is one of the most common chronic neurodegenerative disorders. Despite several in vivo and clinical studies, the cause of the disease is poorly understood. Currently, amyloid β (Aβ) peptide and its tendency to assemble into soluble oligomers are known as a main pathogenic event leading to the interruption of synapses and brain degeneration. Targeting neurotoxic Aβ oligomers can help recognize the disease at an early stage or it can be a potential therapeutic approach. Unnatural β-peptidic foldamers are successfully used against many different protein targets due to their favorable structural and pharmacokinetic properties compared to small molecule or protein-like drug candidates. We have previously reported a tetravalent foldamer-dendrimer conjugate which can selectively bind Aβ oligomers. Taking advantage of multivalency and foldamers, we synthesized different multivalent foldamer-based conjugates to optimize the geometry of the ligand. Isothermal titration calorimetry (ITC) was used to measure binding affinity to Aβ, thereafter 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based tissue viability assay and impedance-based viability assay on SH-SY5Y cells were applied to monitor Aβ toxicity and protective effects of the compounds. Important factors for high binding affinity were determined and a good correlation was found between influencing the valence and the capability of the conjugates for Aβ binding.
LA  - English
DB  - MTMT
ER  -