Issue 35, 2022

Combinatorial synthesis enables scalable designer detergents for membrane protein studies

Abstract

Non-ionic detergents with tailor-made properties are indispensable tools for today's world applications, such as cleaning, disinfection, and drug discovery. To facilitate their challenging production, herein we introduce a new detergent class, namely scalable hybrid detergents. We report a combinatorial synthesis strategy that allows us to fuse head groups of different detergents into hybrid detergents with unbeatable ease. Importantly, combinatorial synthesis also enables the choice between (i) high-throughput preparation of detergents for small scale applications and (ii) large scale preparation of individual detergents. This combinatorial synthesis strategy enables an unprecedented fine tuning of detergent properties, such as overall polarity and shape, which are determining factors in applications, such as membrane protein research. Our data show that membrane protein purification parameters, such as protein yields and activity, can be linked to overall polarity and shape. Conveniently, both parameters can be theoretically described by means of the hydrophilic–lipophilic balance (HLB) and packing parameter concepts. Both concepts are principally applicable to all non-ionic detergent classes, which facilitates the identification of widely applicable design guidelines for the predictable optimization of non-ionic detergents. Our findings permit access to a yet unexplored chemical space of the detergentome, therefore creating new possibilities for structure–property relationship studies. Seen from a broader perspective, combinatorial synthesis will facilitate the preparation of designer detergents with tailor-made properties for future applications in today's world.

Graphical abstract: Combinatorial synthesis enables scalable designer detergents for membrane protein studies

Supplementary files

Article information

Article type
Edge Article
Submitted
01 jun 2022
Accepted
17 aug 2022
First published
30 aug 2022
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., 2022,13, 10299-10307

Combinatorial synthesis enables scalable designer detergents for membrane protein studies

L. H. Urner, A. Ariamajd and A. Weikum, Chem. Sci., 2022, 13, 10299 DOI: 10.1039/D2SC03130B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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