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

Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders. Angew Chem Int Ed Engl. 2018 Apr 12;: Authors: Bunck DN, Atsavapranee B, Museth AK, VanderVelde D, Heath JR Abstract Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death with average survival times of 2 - 5 years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a protein whose stability and aggregation propensity are affected by point mutations spanning the protein. Here, we use an epitope-specific, high-throughput screen to identify peptides that both stabilize the native conformation of SOD1 as well as accelerate its folding by 2.5-fold. Ligands targeted to the electrostatic loop on the periphery of the protein tightened the non-metalated structure and accelerated its folding. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics. PMID: 29645329 [PubMed - as supplied by publisher]
Source: Angewandte Chemie - Category: Chemistry Authors: Tags: Angew Chem Int Ed Engl Source Type: research

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