Protein misfolding diseases are caused by the difficulty of a protein to attain or stably maintain its native three-dimensional structure. In 2011, the first small molecule that specifically binds to the folded state of a protein was approved by a regulatory agency to treat a protein misfolding disease (tafamidis, transthyretin amyloidosis). Subsequently, folded state binders for three additional pathologies were approved. All of these molecules bind specifically to and stabilize the native state of a misfolding-prone protein and either correct cellular folding or stabilize the native state against misfolding and aggregation. We will use these four case studies to explain how protein folding coupled to small molecule binding is a promising approach to treat a variety of human maladies.

Small molecule protein binding to correct cellular folding or stabilize the native state against misfolding and aggregation / Chiti, Fabrizio; Kelly, Jeffery W. - In: CURRENT OPINION IN STRUCTURAL BIOLOGY. - ISSN 0959-440X. - STAMPA. - 72:(2022), pp. 267-278. [10.1016/j.sbi.2021.11.009]

Small molecule protein binding to correct cellular folding or stabilize the native state against misfolding and aggregation

Chiti, Fabrizio
;
2022

Abstract

Protein misfolding diseases are caused by the difficulty of a protein to attain or stably maintain its native three-dimensional structure. In 2011, the first small molecule that specifically binds to the folded state of a protein was approved by a regulatory agency to treat a protein misfolding disease (tafamidis, transthyretin amyloidosis). Subsequently, folded state binders for three additional pathologies were approved. All of these molecules bind specifically to and stabilize the native state of a misfolding-prone protein and either correct cellular folding or stabilize the native state against misfolding and aggregation. We will use these four case studies to explain how protein folding coupled to small molecule binding is a promising approach to treat a variety of human maladies.
72
267
278
Chiti, Fabrizio; Kelly, Jeffery W
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1284770
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