Design and Synthesis of Small Molecule Ligands to stabilize SOD1 Variants Combating Amyotrophic Lateral Sclerosis

Research - Roman Graebner

Amyotrophic lateral sclerosis (ALS) is a currently incurable neurodegenerative disease. The underlying biochemical mechanisms leading to the onset and progression of this vicious disease are the subject of current research.

Mutations of the Cu/Zn superoxide dismutase SOD1 associated with destabilization of this dimer protein and its aggregation have been observed in a proportion of affected individuals. The stabilization of SOD1 by means of rationally designed organic small molecules is the focus of my research.

Using molecular docking as a computational screening method, a series of promising ligands derived from a common lead structure have been proposed. The modular synthesis developed for these ligands allows for the convenient preparation of a compound library. Naturally, synthetic organic chemistry builds the foundation for my research.

A number of biophysical assays are used to study protein-ligand interactions. Therefore, optimization of existing assays and establishment of suitable novel assays is another cornerstone of my work.

With this research, we hope to contribute to the elucidation of the underlying mechanisms of ALS and the development of desperately needed future medical treatments.