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

Angew Chem Int Ed Engl. 2018 May 22;57(21):6212-6215. doi: 10.1002/anie.201802269. Epub 2018 Apr 25.

Abstract

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.

Keywords: high-throughput screening; neurodegenerative diseases; peptides; protein folding; superoxide dismutase 1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Peptides, Cyclic / chemistry*
  • Protein Folding
  • Superoxide Dismutase-1 / chemistry*
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism

Substances

  • Ligands
  • Peptides, Cyclic
  • SOD1 protein, human
  • Superoxide Dismutase-1