Dendritic Detergents for the Analysis of Proteins by Mass Spectrometry

Simple SummaryContent extracted from patent full text and abstract with AI.

The patent describes the use of specially designed dendritic detergents to improve the extraction, stabilization, and analysis of proteins, particularly membrane proteins, by mass spectrometry (MS). These dendritic detergents, featuring a branched, polyhydroxylated head and a hydrophobic tail, facilitate the extraction of proteins from their native membranes, maintain their structural integrity, and enable more accurate and sensitive detection in MS-based analysis. The detergents can be tuned to different applications, such as preserving protein-ligand interactions or optimizing charge states for MS.

Use CasesContent extracted from patent full text and abstract with AI.

• Extraction and purification of membrane proteins from native cell membranes for research or industrial purposes.
• Structural analysis of membrane proteins and protein complexes (including those bound to ligands or drugs) by mass spectrometry.
• Screening for drug-protein interactions, including the binding of potential therapeutic agents to protein targets.
• Improvement of native mass spectrometry (MS) studies by preserving functional protein states and reducing artifacts.
• Analysis of soluble proteins, especially in cases of sample contamination with alkali metals or other salts.
• Pharmaceutical development, including direct observation of drug binding to target proteins in their native-like states.

BenefitsContent extracted from patent full text and abstract with AI.

• Enhanced extraction of membrane proteins in their intact, functional (native) conformations, overcoming previous challenges with traditional detergents.
• Preservation of protein-ligand complexes during MS analysis, enabling more accurate studies of interactions with drugs or endogenous molecules.
• Tunability of detergent properties allows for adjustment to specific experimental needs (e.g., charge state control, preserving lipid binding, etc.).
• Improved sensitivity and signal quality in mass spectrometry, including better resolution and less peak broadening from alkali metal contamination.
• Facilitation of direct, rapid MS-based screening of protein-ligand or protein-drug interactions without the need for extensive protein crystallization or labeling.
• Compatibility with a broad range of proteins, including both membrane and soluble proteins, increasing the versatility of the approach.

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Patent Abstract

A method of detecting a protein by mass spectrometry comprises: providing a solution comprising a dendritic detergent and a protein; providing a mass spectrometer comprising a nanoelectrospray ionisation source, a mass analyser and a detector; vaporising the solution using the nanoelectrospray ionisation source; ionising the protein; resolving the ionised protein using the mass analyser; and detecting the resolved protein using the detector. A method of extracting a membrane protein from its native membrane comprises: providing a membrane protein in its native membrane; contacting the membrane protein with a dendritic detergent. Dendritic detergents for use in the methods are also provided.