Amystap

Project: Amino Acid–Based Ligands as Stabilizers of Amyloidogenic Proteins

The project is focused on studying the interactions between amyloidogenic proteins and amino acid-based ligands (AA-ligands) with the aim of identifying compounds capable of stabilizing the native structure of proteins and suppressing their amyloid aggregation. Amyloid aggregation of proteins is associated with several serious diseases (e.g., Alzheimer’s disease) and at the same time represents a significant issue in the stability of biotechnologically used proteins such as insulin and α-lactalbumin.


Main objective of the project

The main objective of the project is to identify AA-ligands that:
• effectively inhibit the formation of amyloid aggregates,
• stabilize the native conformation of proteins,
• demonstrate biocompatibility and potential for further development.

The project focuses on amyloid β peptide, lysozyme, insulin, and α-lactalbumin. Three types of amino acid-based ligands will be investigated:
• organic salts (AA-OS),
• polypeptides (AA-PP),
• amino acid-modified nanoparticles (AA-NP).

Specific objectives

• Characterization of prepared AA-ligands in terms of their physicochemical properties, stability, and cytotoxicity.
• Identification of ligands with inhibitory effects on amyloid aggregation using spectroscopic and microscopic methods.
• Selection of AA-ligands capable of stabilizing the native structure of proteins.
• Proposal of the interaction mechanism between the AA-ligand and the protein.
• Verification of the effectiveness of selected ligands in more complex in vitro model systems simulating biological environments.

Expected project outcomes

The project will result in:
• a library of stable and non-toxic AA-ligands with anti-amyloid activity,
• identification of ligands capable of stabilizing the native conformation of proteins,
• proposal of mechanisms of action leading to inhibition of amyloid aggregation,
• selection of biocompatible candidates suitable for further preclinical and clinical studies,
• strengthening of international scientific collaboration and increasing the competitiveness of the research team.

The project will also contribute to the advancement of knowledge in the field of protein stability, misfolding, and amyloid aggregation, which have significant impact on healthcare and biotechnological applications.

Project funding

The project is co-funded by the European Union under the Programme Slovakia.

Financial support from EU funds enables the implementation of high-level research, infrastructure development, international collaboration, and support of the research team in addressing current challenges in the field of neurodegenerative diseases and stability of therapeutic proteins.