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Designed glycopeptidomimetics disrupt protein-protein interactions mediating amyloid β-peptide aggregation and restore neuroblastoma cell viability ACS Paragon Plus Environment Journal of Medicinal Chemistry Designed glycopeptidomimetics disrupt protein-protein interactions mediating amyloid β-peptide aggregation and restore neuroblastoma cell viability

Julia Kaffy, Dimitri Brinet, Jean-Louis Soulier, Isabelle Correia, Nicolo Tonali, Katia Fera, Yasmine Iacone, Anaïs Hoffmann, Lucie Khemtémourian, Benoit Crousse, Mark Taylor, David Allsop (+3 others)
Journal: Journal of Medicinal Chemistry   unpublished

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How anti-Alzheimer's drug candidates that reduce amyloid 1-42 peptide fibrillization interact with the most neurotoxic species is far from being understood. We report herein the capacity of sugar-based peptidomimetics to inhibit both Aβ 1-42 early oligomerization and fibrillization. A wide range of bio-and physico-chemical techniques, such as a new capillary electrophoresis method, nuclear magnetic resonance, and surface plasmon resonance, were used to identify how these new molecules can delay
more » ... the aggregation of Aβ 1-42. We demonstrate that these molecules interact with soluble oligomers in order to maintain the presence of non-toxic monomers and to prevent fibrillization. These compounds totally suppress the toxicity of Aβ 1-42 towards SH-SY5Y neuroblastoma cells, even at sub-stoichiometric concentrations. Furthermore, demonstration that the best molecule combines hydrophobic moieties, hydrogen bond donors and acceptors, ammonium groups and a hydrophilic β-sheet breaker element, provides valuable insight for the future structure-based design of inhibitors of Aβ 1-42 aggregation.
fatcat:akaq34mb5rhrvi5gyn2npep654
Citation

Julia Kaffy, Dimitri Brinet, Jean-Louis Soulier, Isabelle Correia, Nicolo Tonali, Katia Fera, Yasmine Iacone, Anaïs Hoffmann, Lucie Khemtémourian, Benoit Crousse, Mark Taylor, David Allsop, Myriam Taverna, Olivier Lequin, Sandrine Ongeri. "Designed glycopeptidomimetics disrupt protein-protein interactions mediating amyloid β-peptide aggregation and restore neuroblastoma cell viability ACS Paragon Plus Environment Journal of Medicinal Chemistry Designed glycopeptidomimetics disrupt protein-protein interactions mediating amyloid β-peptide aggregation and restore neuroblastoma cell viability." Journal: Journal of Medicinal Chemistry