Issue 7, 2024

Enzymatic and synthetic regulation of polypeptide folding


Proper folding is essential for the biological functions of all proteins. The folding process is intrinsically error-prone, and the misfolding of a polypeptide chain can cause the formation of toxic aggregates related to pathological outcomes such as neurodegenerative disease and diabetes. Chaperones and some enzymes are involved in the cellular proteostasis systems that assist polypeptide folding to diminish the risk of aggregation. Elucidating the molecular mechanisms of chaperones and related enzymes is important for understanding proteostasis systems and protein misfolding- and aggregation-related pathophysiology. Furthermore, mechanistic studies of chaperones and related enzymes provide important clues to designing chemical mimics, or chemical chaperones, that are potentially useful for recovering proteostasis activities as therapeutic approaches for treating and preventing protein misfolding-related diseases. In this Perspective, we provide a comprehensive overview of the latest understanding of the folding-promotion mechanisms by chaperones and oxidoreductases and recent progress in the development of chemical mimics that possess activities comparable to enzymes, followed by a discussion of future directions.

Graphical abstract: Enzymatic and synthetic regulation of polypeptide folding

Article information

Article type
29 Oct 2023
04 Jan 2024
First published
26 Jan 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2024,15, 2282-2299

Enzymatic and synthetic regulation of polypeptide folding

T. Muraoka, M. Okumura and T. Saio, Chem. Sci., 2024, 15, 2282 DOI: 10.1039/D3SC05781J

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