Foldable detergents for membrane protein study: Importance of detergent core flexibility in protein stabilization

Research output: Contribution to journalJournal articleResearchpeer-review


  • Fulltext

    Accepted author manuscript, 1.43 MB, PDF document

Membrane proteins are of biological and pharmaceutical significance. However, their structural study is extremely challenging mainly due to the fact that only a small number of chemical tools is suitable for stabilizing membrane proteins in solution. Detergents are widely used in membrane protein study, but conventional detergents are generally poor at stabilizing challenging membrane proteins such as G protein-coupled receptors and protein complexes. In the current study, we prepared tandem triazine-based maltosides (TZMs) with two amphiphilic triazine units connected by different diamine linkers, hydrazine (TZM-Hs) and 1,2-ethylenediamine (TZM-Es). These TZMs were consistently superior to a gold standard detergent (DDM) in terms of stabilizing a few membrane proteins. In addition, the TZM-Es containing a long linker showed more general protein stabilization efficacy with multiple membrane proteins than the TZM-Hs containing a short linker. This result indicates that introduction of the flexible1,2-ethylenediamine linker between two rigid triazine rings enables the TZM-Es to fold into favourable conformations in order to promote membrane protein stability. The novel concept of detergent foldability introduced in the current study has potential use for rational detergent design and membrane protein applications.

Original languageEnglish
Article numbere202200116
JournalChemistry: A European Journal
Issue number21
Number of pages9
Publication statusPublished - 2022

Bibliographical note

© 2022 Wiley-VCH GmbH.

ID: 299388785