Method for Sequencing Peptides and Proteins Using Metastable-Activated Dissociation Mass Spectrometry

Abstract

Methods for fragmentation of large molecular ions, including proteins, nucleic acids, dendromers, and nanomaterials, compatible with several mass spectrometric techniques. The methods involve providing a gas-phase ion and allowing the gas phase ion to undergo collisions with metastable states of noble gases or nitrogen gas.

1 . A method for fragmenting macromolecules in the gas phase, the method comprising the steps of providing metastable atoms and colliding the macromolecular ions with the metastable atoms. 
   
   
       2 . The method of  claim 1  wherein the macromolecules are collided with the metastable atoms in a mass spectrometer. 
   
   
       3 . The method of  claim 2  wherein the mass spectrometer is a quadrupole ion trap mass spectrometer. 
   
   
       4 . The method of any one of  claims 1 - 3  wherein macromolecules are selected from the group consisting of peptides, proteins, nucleic acids, dendodromers, and nanomaterials. 
   
   
       5 . The method of any one of  claims 1 - 4  wherein the macromolecules have a molecular weight greater than about 3 kD. 
   
   
       6 . The method of any one of  claims 1 - 5  wherein the metastable atoms are selected from metastable nitrogen atoms and metastable noble gases. 
   
   
       7 . The method of  claim 6  wherein the metastable noble gases are selected from metastable helium, metastable neon, and metastable argon. 
   
   
       8 . The method of any one of  claims 1 - 7  wherein the macromolecules are neutral. 
   
   
       9 . The method of any one of  claims 1 - 7  wherein the macromolecules are positively charged ions. 
   
   
       10 . The method of any one of  claims 1 - 7  wherein the macromolecules are negatively charged ions. 
   
   
       11 . A method for activating macromolecules in the gas phase comprising the steps of providing metastable atoms and colliding the macromolecular ions with the metastable atoms. 
   
   
       12 . The method of  claim 11  wherein the activation results in dissociation of the macromolecule. 
   
   
       13 . The method of  claim 12  wherein the macromolecule is selected from the group consisting of peptides, proteins, nucleic acids, dendodromers, and nanomaterials. 
   
   
       14 . The method of  claim 13  wherein the macromolecules have a molecular weight of greater than about 3 kDa. 
   
   
       15 . A system capable of directly determining the amino acid sequence of large peptides and proteins comprising a mass spectrometer and a source of metastable atoms and a detector, wherein the large proteins or peptides collide with the metastable ions and fragment and the fragments are detected by the detector. 
   
   
       16 . The system of  claim 15  wherein the mass spectrometer is a quadrupole mass spectrometer.