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Title: Structural determination of intact proteins using mass spectrometry

Abstract

The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

Inventors:
 [1];  [2];  [3]
  1. San Francisco, CA
  2. Oakland, CA
  3. Livermore, CA
Issue Date:
Research Org.:
Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
936326
Patent Number(s):
7368290
Application Number:
10/437,268
Assignee:
Sandia National Laboratories (Livermore, CA)
Patent Classifications (CPCs):
G - PHYSICS G01 - MEASURING G01N - INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
DOE Contract Number:  
AC04-94AL85000
Resource Type:
Patent
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Kruppa, Gary, Schoeniger, Joseph S, and Young, Malin M. Structural determination of intact proteins using mass spectrometry. United States: N. p., 2008. Web.
Kruppa, Gary, Schoeniger, Joseph S, & Young, Malin M. Structural determination of intact proteins using mass spectrometry. United States.
Kruppa, Gary, Schoeniger, Joseph S, and Young, Malin M. Tue . "Structural determination of intact proteins using mass spectrometry". United States. https://www.osti.gov/servlets/purl/936326.
@article{osti_936326,
title = {Structural determination of intact proteins using mass spectrometry},
author = {Kruppa, Gary and Schoeniger, Joseph S and Young, Malin M},
abstractNote = {The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {2008},
month = {5}
}

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Works referenced in this record:

A top down approach to protein structural studies using chemical cross-linking and Fourier transform mass spectrometry
journal, January 2003


?Top down? protein characterization via tandem mass spectrometry
journal, January 2002


Protein mass spectrometry: applications to analytical biotechnology
journal, June 1995


High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry
journal, May 2000


Top Down versus Bottom Up Protein Characterization by Tandem High-Resolution Mass Spectrometry
journal, February 1999


Constrained walks and self-avoiding walks: implications for protein structure determination
journal, December 2001