Interactions of selected ligands with biomolecules of medicinal interest in Alzheimer disease, mediated by essential metal ions.

• Grant number: 20/06719-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2022
• End date: November 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Ana Maria da Costa Ferreira
• Grantee: Ana Paula Araujo de Oliveira
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Herein, we intend to investigate molecular interactions of imine ligands, containing indole, hydrazone or thiosemicarbazone moieties, with biomolecules of medicinal interest especially peptides and proteins implicated in Alzheimer disease (AD). Imine ligands derived from oxindoles have shown, in previous studies in our lab, strong binding to these b-amyloid peptides, causing substantial inhibition in the aggregation of such peptides, in the presence of copper(II) or zinc(II) ions, that favored this aggregation. The ligands to be investigated will be designed to act as good coordinating agents to transition metal ions, forming complex species thermodynamically stable (with high values of formation constants). We intend particularly to verify how the metal ions are inserted in the formed complex (metal-ligand)-peptide adduct, monitoring those interactions mainly by spectroscopic methods (RMN, EPR, CD) and mass spectrometry. If possible, the researcher Ana Paula will spend a period at the University of Manchester, to realize experiments more advanced at the National UK EPR Facility and Service, under supervision of Dr. Floriana Tuna, with whom we have collaboration since 2017. The proposed investigations will improve our knowledge about possible modes of action of the metal complexes studied, mainly of copper(II) and zinc(II), at the aim of the development of novel metallodrugs, based on their reactivity toward peptides.