Description:

 

INV-0940

Background

Sensitive analytical tools are needed for the rapid characterization of conformations of both small globular proteins and large macromolecular complexes. Characterization of non-native conformational structures, including misfolded proteins and aggregated proteins is highly important in the detection of a variety of diseases with such pathophysiology, including neurodegenerative diseases. Ion mobility spectrometry techniques are valuable tools that help to separate complex mixtures and to determine structural information. There are different ion mobility spectrometry methods among which traveling-wave ion mobility spectrometry (TWIMS) is one of the newest ones that is well integrated into commercial mass spectrometers, thus it has become markedly distinct from prior techniques. Despite the mentioned benefits, TWIMS has the lowest resolving power of all ion mobility spectrometry and still needs further development in terms of separation selectivity. 

Technology Overview

Researchers at Northeastern developed a new method that utilizes sequential ion mobility and rapid deuterium labeling in a traveling wave ion guide (TWIG) to produce high-resolution detection of gaseous protein conformations. They demonstrated that a TWIG of a mass spectrometer offers a highly suitable environment for rapid and efficient gas-phase hydrogen/deuterium exchange (HDX). In this method, gaseous ND3 is introduced into either the source TWIG or the TWIG located just after the ion mobility cell, such that ions undergo HDX as they pass through the ND3 on the way to the time-of-flight analyzer. The extent of deuterium labeling can be controlled by varying the quantity of ND3 or the speed of the traveling wave. The gas-phase HDX of model peptides corresponds to the labeling of primarily fast exchanging sites due to the short labeling times. This method of labeling reports on the shape, surface reactivity, and intramolecular hydrogen bonding of conformations thereby enhancing detection of conformations of small proteins and protein complexes at native conditions. Also, unlike conventional methods that require high-pressure, this method yields high-resolution results in low-pressure environments. Taken together, HDX of protein ions combined with TWIMS is highly sensitive to protein conformation and enables the detection of conformers in less than milliseconds. 

Benefits

  • High-resolution detection 
  • Possibility of labeling in a low-pressure environment 
  • Possibility of combining with a wide range of mass spectrometric techniques
  • Rapid detection 

Applications

  • Detection of protein aggregation in different diseases such as Huntington’s, Alzheimer’s, Parkinson’s, Diabetes, Rheumatoid arthritis, Atherosclerosis, Cardiac arrhythmias, Carcinomas
  • Determining stoichiometry of large functional protein assemblies 

Opportunity

  • License
  • Partnering
  • Research collaboration
Patent Information:
For Information, Contact:
Mark Saulich
Associate Director of Commercialization
Northeastern University
m.saulich@northeastern.edu
Inventors:
John Engen
Kasper Dryberg Rand
Keywords:
Chemistry
Detection