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Modulating SOD1 Folding Landscapes with Targeted Molecular Binders

Bunck, David N. and Atsavapranee, Beatriz and Museth, Katrine and Heath, James (2017) Modulating SOD1 Folding Landscapes with Targeted Molecular Binders. Biophysical Journal, 112 (3, Supp. 1). 168a. ISSN 0006-3495. https://resolver.caltech.edu/CaltechAUTHORS:20170623-103813691

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Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the deterioration of motor neurons that abates essential biological functions and exhibits survival times of 3 - 5 years after diagnosis. One driver of this disease derives from inherited mutations to the protein superoxide dismutase 1 (SOD1), which hinder proper folding and result in the accumulation of toxic aggregates. We identified cyclic peptides that target precise epitopes on SOD1 through an emerging screening platform that furnishes high-affinity binders against regions of a protein independent of secondary or tertiary structure. Binding these epitopes both stabilizes the native state and accelerates folding. In this context, these small peptides function as molecular chaperones and mitigate the impact of deleterious mutations to SOD1. They also display the traditional benefits of small molecules, such as straightforward chemical modifications and long-term stability. Overall, this method provides a route to rationally perturb the energy landscape of any protein through noncovalent binding, making it useful in fundamental studies of protein folding as well as designing therapeutics for misfolding diseases.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.bpj.2016.11.928DOIArticle
http://www.sciencedirect.com/science/article/pii/S0006349516319580PublisherArticle
ORCID:
AuthorORCID
Heath, James0000-0001-5356-4385
Additional Information:© 2017 Elsevier B.V. Available online 3 February 2017. Meeting Abstract: 829-Plat.
Issue or Number:3, Supp. 1
Record Number:CaltechAUTHORS:20170623-103813691
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170623-103813691
Official Citation:David N. Bunck, Beatriz Atsavapranee, Katrine Museth, James Heath, Modulating SOD1 Folding Landscapes with Targeted Molecular Binders, Biophysical Journal, Volume 112, Issue 3, Supplement 1, 3 February 2017, Page 168a, ISSN 0006-3495, https://doi.org/10.1016/j.bpj.2016.11.928. (http://www.sciencedirect.com/science/article/pii/S0006349516319580)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:78514
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Jun 2017 03:04
Last Modified:03 Oct 2019 18:09

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