Ligand-Induced Stabilization of the Native Human Superoxide Dismutase 1

نویسندگان

چکیده

A common characteristic of familial (fALS) and sporadic amyotrophic lateral sclerosis (sALS) is the accumulation aberrant proteinaceous species in motor neurons spinal cord ALS patients—including aggregates human superoxide dismutase 1 (hSOD1). hSOD1 an enzyme that occurs as a stable dimeric protein with several post-translational modifications such formation intramolecular disulfide bond acquisition metal cofactors are essential for activity further contribute to stability. Some mutations and/or destabilizing factors promote misfolding, causing neuronal death. Aggregates containing misfolded wild-type have been found cords sALS well non-hSOD1 fALS patients, leading hypothesis misfolding part pathomechanism. Therefore, stabilizing native conformation SOD1 may be promising approach prevent toxic thus pathogenesis. Here, we present 16-mer peptide S1VL-21 interferes aggregation. was identified by phage display selection target. Several methods microscale thermophoresis (MST) measurements, aggregation assays, cell viability assays revealed has micromolar binding affinity considerably reduces aggregates. This work therefore provides first important data on potential lead compound hSOD1-related drug development therapy.

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ژورنال

عنوان ژورنال: ACS Chemical Neuroscience

سال: 2021

ISSN: ['1948-7193']

DOI: https://doi.org/10.1021/acschemneuro.1c00253