Exploring the Potential of Dendritic Oligoglycerol Detergents for Protein Mass Spectrometry

Abstract

The ability to design detergents that are suitable for protein analysis by mass spectrometry (MS) represents an on-going challenge in the field of native MS. Desirable detergent characteristics include charge-reducing properties and low gas-phase stabilities of complexes formed with proteins. In this work, the gas-phase properties of oligoglycerol detergents (OGDs) are optimized by fine tuning of their molecular structure. Furthermore, a tandem mass spectrometry (MS/MS) approach is presented that estimates the gas-phase properties of detergents simply by studying the dissociation behaviour of protein-detergent complexes (PDCs) formed with the soluble protein β-lactoglobulin (BLG). Graphical Abstractᅟ Electronic supplementary materialThe online version of this article (10.1007/s13361-018-2063-2) contains supplementary material, which is available to authorized users.

Modular detergents tailor the purification and structural analysis of membrane proteins including G-protein coupled receptors

“…In addition, we reasoned that changing the basicity of the linker between the OGD head and tail, e.g. ether/carbamate < triazole, would allow us to effectively tune charge states of membrane proteins in mass spectra-a feature that is of enormous interest within the emerging native MS community [20][21][22][23][24] . Having synthesized these detergents we now evaluate their ability to extract membrane proteins, retain subunit interactions, and lipid binding properties, as well as to produce favorable characteristics for native mass spectra.…”

“…3b). This charge reduction is expected because the ability of the linker to abstract charges (mainly protons) from protein ions is directly related to its basicity 23 . The z ave obtained from the [G1] OGD regioisomer mixture 2 (15+) was lower than the value obtained from the charge-reducing detergent C8E4 (17.5+, Supplementary Figs.…”

A new azobenzene-based design strategy for detergents in membrane protein research

“…The basicity of detergents has recently been identied as a key parameter for controlling charge reduction in membrane protein mass spectrometry. 7,59 This prompted an important question. Can azobenzene detergents be used for controlling protein charge reduction by light?…”

“…2 Protein charge reduction has been identied as a key parameter in this process, because it lowers the disruptive impact of Coulomb interactions on protein structure. [3][4][5] Protein charge reduction can be achieved in many ways, for example, by using basic solution additives, [3][4][5] detergents, 4,6,7 or by treating the electrospray plume with acetonitrile vapour. 3 The extent of charge reduction that is needed for retaining native structural features of a protein complex is difficult to generalize and needs to be determined experimentally.…”

“…6,8 Detergent designers are therefore faced with the challenge to identify design rules that allow to compromise the protein-compatibility of detergents in solution and their charge-reducing properties in the gas phase. 7 Generally, detergents are of limited use when the intended application requires their properties to be dynamically altered during the application. To enable such remote control, detergents are oen modied with azobenzene, which consists of two phenyl rings that are held together by a N]N bond.…”