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Noncovalent modulation of protien energy landscapes with targeted molecular binders

Bunck, David and Atsavapranee, Beatriz and Museth, Katrine and Vander Velde, David and Heath, James (2017) Noncovalent modulation of protien energy landscapes with targeted molecular binders. In: 254th American Chemical Society National Meeting & Exposition, August 20-24, 2017, Washington, DC.

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the deterioration of motor neurons that abates essential biol. 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 and tertiary structure. Binding these epitopes both stabilizes the native state and accelerates folding. In this context, these small peptides function as mol. chaperones and mitigate the impact of deleterious mutations to SOD1. They also display the traditional benefits of small mols., such as straightforward chem. 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:Conference or Workshop Item (Paper)
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URLURL TypeDescription Website
Bunck, David0000-0002-6246-9846
Vander Velde, David0000-0002-2907-0366
Heath, James0000-0001-5356-4385
Additional Information:© 2017 American Chemical Society.
Record Number:CaltechAUTHORS:20170913-105300196
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:81411
Deposited By: Tony Diaz
Deposited On:14 Sep 2017 02:35
Last Modified:09 Mar 2020 13:19

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