Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders

Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death, with average survival times of two to five years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a phenomenon influenced by point mutations spanning the protein. Herein, we used an epitope‐specific high‐throughput screen to identify a peptide ligand that stabilizes the SOD1 native conformation and accelerates its folding by a factor of 2.5. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics.

David N. Bunck, Beatriz Atsavapranee, Anna K. Museth, David VanderVelde and James R. Heath
Angewandte Chemie
Volume: 130
Number: 121
Pages: 6320-6323
Date: May, 2018
ICB Affiliated Authors: James R Heath